Feasibility of RACT for 3D dose measurement and range verification in a water phantom.

PubMed

Alsanea, Fahed; Moskvin, Vadim; Stantz, Keith M

2015-02-01

The objective of this study is to establish the feasibility of using radiation-induced acoustics to measure the range and Bragg peak dose from a pulsed proton beam. Simulation studies implementing a prototype scanner design based on computed tomographic methods were performed to investigate the sensitivity to proton range and integral dose. Derived from thermodynamic wave equation, the pressure signals generated from the dose deposited from a pulsed proton beam with a 1 cm lateral beam width and a range of 16, 20, and 27 cm in water using Monte Carlo methods were simulated. The resulting dosimetric images were reconstructed implementing a 3D filtered backprojection algorithm and the pressure signals acquired from a 71-transducer array with a cylindrical geometry (30 × 40 cm) rotated over 2π about its central axis. Dependencies on the detector bandwidth and proton beam pulse width were performed, after which, different noise levels were added to the detector signals (using 1 μs pulse width and a 0.5 MHz cutoff frequency/hydrophone) to investigate the statistical and systematic errors in the proton range (at 20 cm) and Bragg peak dose (of 1 cGy). The reconstructed radioacoustic computed tomographic image intensity was shown to be linearly correlated to the dose within the Bragg peak. And, based on noise dependent studies, a detector sensitivity of 38 mPa was necessary to determine the proton range to within 1.0 mm (full-width at half-maximum) (systematic error < 150 μm) for a 1 cGy Bragg peak dose, where the integral dose within the Bragg peak was measured to within 2%. For existing hydrophone detector sensitivities, a Bragg peak dose of 1.6 cGy is possible. This study demonstrates that computed tomographic scanner based on ionizing radiation-induced acoustics can be used to verify dose distribution and proton range with centi-Gray sensitivity. Realizing this technology into the clinic has the potential to significantly impact beam commissioning, treatment verification during particle beam therapy and image guided techniques.

Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuaron, John J.; Chon, Brian; Tsai, Henry

Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered wasmore » 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary toxicities.« less

Treatment Plan Technique and Quality for Single-Isocenter Stereotactic Ablative Radiotherapy of Multiple Lung Lesions with Volumetric-Modulated Arc Therapy or Intensity-Modulated Radiosurgery

PubMed Central

Quan, Kimmen; Xu, Karen M.; Lalonde, Ron; Horne, Zachary D.; Bernard, Mark E.; McCoy, Chuck; Clump, David A.; Burton, Steven A.; Heron, Dwight E.

2015-01-01

The aim of this study is to provide a practical approach to the planning technique and evaluation of plan quality for the multi-lesion, single-isocenter stereotactic ablative radiotherapy (SABR) of the lung. Eleven patients with two or more lung lesions underwent single-isocenter volumetric-modulated arc therapy (VMAT) radiosurgery or IMRS. All plans were normalized to the target maximum dose. For each plan, all targets were treated to the same dose. Plan conformity and dose gradient were maximized with dose-control tuning structures surrounding targets. For comparison, multi-isocenter plans were retrospectively created for four patients. Conformity index (CI), homogeneity index (HI), gradient index (GI), and gradient distance (GD) were calculated for each plan. V5, V10, and V20 of the lung and organs at risk (OARs) were collected. Treatment time and total monitor units (MUs) were also recorded. One patient had four lesions and the remainder had two lesions. Six patients received VMAT and five patients received intensity-modulated radiosurgery (IMRS). For those treated with VMAT, two patients received 3-arc VMAT and four received 2-arc VMAT. For those treated with IMRS, two patients were treated with 10 and 11 beams, respectively, and the rest received 12 beams. Prescription doses ranged from 30 to 54 Gy in three to five fractions. The median prescribed isodose line was 84% (range: 80–86%). The median maximum dose was 57.1 Gy (range: 35.7–65.1 Gy). The mean combined PTV was 49.57 cm3 (range: 14.90–87.38 cm3). For single-isocenter plans, the median CI was 1.15 (range: 0.97–1.53). The median HI was 1.19 (range: 1.16–1.28). The median GI was 4.60 (range: 4.16–7.37). The median maximum radiation dose (Dmax) to total lung was 55.6 Gy (range: 35.7–62.0 Gy). The median mean radiation dose to the lung (Dmean) was 4.2 Gy (range: 1.1–9.3 Gy). The median lung V5 was 18.7% (range: 3.8–41.3%). There was no significant difference in CI, HI, GI, GD, V5, V10, and V20 (lung, heart, trachea, esophagus, and spinal cord) between single-isocenter and multi-isocenter plans. This multi-lesion, single-isocenter lung SABR planning technique demonstrated excellent plan quality and clinical efficiency and is recommended for radiosurgical treatment of two or more lung targets for well-suited patients. PMID:26500888

Site-specific range uncertainties caused by dose calculation algorithms for proton therapy

NASA Astrophysics Data System (ADS)

Schuemann, J.; Dowdell, S.; Grassberger, C.; Min, C. H.; Paganetti, H.

2014-08-01

The purpose of this study was to assess the possibility of introducing site-specific range margins to replace current generic margins in proton therapy. Further, the goal was to study the potential of reducing margins with current analytical dose calculations methods. For this purpose we investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict the range of proton fields. Dose distributions predicted by an analytical pencil-beam algorithm were compared with those obtained using Monte Carlo (MC) simulations (TOPAS). A total of 508 passively scattered treatment fields were analyzed for seven disease sites (liver, prostate, breast, medulloblastoma-spine, medulloblastoma-whole brain, lung and head and neck). Voxel-by-voxel comparisons were performed on two-dimensional distal dose surfaces calculated by pencil-beam and MC algorithms to obtain the average range differences and root mean square deviation for each field for the distal position of the 90% dose level (R90) and the 50% dose level (R50). The average dose degradation of the distal falloff region, defined as the distance between the distal position of the 80% and 20% dose levels (R80-R20), was also analyzed. All ranges were calculated in water-equivalent distances. Considering total range uncertainties and uncertainties from dose calculation alone, we were able to deduce site-specific estimations. For liver, prostate and whole brain fields our results demonstrate that a reduction of currently used uncertainty margins is feasible even without introducing MC dose calculations. We recommend range margins of 2.8% + 1.2 mm for liver and prostate treatments and 3.1% + 1.2 mm for whole brain treatments, respectively. On the other hand, current margins seem to be insufficient for some breast, lung and head and neck patients, at least if used generically. If no case specific adjustments are applied, a generic margin of 6.3% + 1.2 mm would be needed for breast, lung and head and neck treatments. We conclude that the currently used generic range uncertainty margins in proton therapy should be redefined site specific and that complex geometries may require a field specific adjustment. Routine verifications of treatment plans using MC simulations are recommended for patients with heterogeneous geometries.

Evaluation of 16 genotype-guided Warfarin Dosing Algorithms in 310 Korean Patients Receiving Warfarin Treatment: Poor Prediction Performance in VKORC1 1173C Carriers.

PubMed

Yang, Mina; Choi, Rihwa; Kim, June Soo; On, Young Keun; Bang, Oh Young; Cho, Hyun-Jung; Lee, Soo-Youn

2016-12-01

The purpose of this study was to evaluate the performance of 16 previously published warfarin dosing algorithms in Korean patients. The 16 algorithms were selected through a literature search and evaluated using a cohort of 310 Korean patients with atrial fibrillation or cerebral infarction who were receiving warfarin therapy. A large interindividual variation (up to 11-fold) in warfarin dose was observed (median, 25 mg/wk; range, 7-77 mg/wk). Estimated dose and actual maintenance dose correlated well overall (r range, 0.52-0.73). Mean absolute error (MAE) of the 16 algorithms ranged from -1.2 to -20.1 mg/wk. The percentage of patients whose estimated dose fell within 20% of the actual dose ranged from 1.0% to 49%. All algorithms showed poor accuracy with increased MAE in a higher dose range. Performance of the dosing algorithms was worse in patients with VKORC1 1173TC or CC than in total (r range, 0.38-0.61 vs 0.52-0.73; MAE range, -2.6 to -28.0 mg/wk vs -1.2 to -20.1 mg/wk). The algorithms had comparable prediction abilities but showed limited accuracy depending on ethnicity, warfarin dose, and VKORC1 genotype. Further studies are needed to develop genotype-guided warfarin dosing algorithms with greater accuracy in the Korean population. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Results of daily oral dosing with up to 60,000 international units (iu) of vitamin D3 for 2 to 6 years in 3 adult males.

PubMed

McCullough, Patrick; Amend, Jeffrey

2017-10-01

In the 1930's and 1940's, vitamin D was reported to be an effective treatment for a number of diseases, including asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. High doses were used, 60,000 to 300,000 IU a day for asthma, and 200,000 to 600,000 IU a day for rheumatoid arthritis. Toxicity from hypercalcemia occurred after prolonged oral dosing with these supraphysiologic doses. Assays for measuring vitamin D in the blood were not available, and blood levels of vitamin D associated with hypercalcemia were unknown. A 2011 report on vitamin D toxicity showed that hypercalcemia resolved when 25-hydroxyvitamin D (25OHD) blood levels dropped below 400ng/ml in 2 patients with blood levels ranging from 645ng/ml to 1220ng/ml after accidental ingestion of massive doses of vitamin D. We now know that vitamin D is made in the skin in amounts ranging up to 25,000 IU a day with exposure to UVB radiation. There is little data on the safety and blood levels of 25OHD and calcium after prolonged daily intake of amounts of vitamin D in this range. In this report, one subject took increasing daily doses of vitamin D3 for 6 years starting in April 2009: 6500 IU for 6 months; increasing to 10,000 IU for 13 months; 20,000 IU for 24 months; 40,000 IU for 12 months; 50,000 IU for 10 months, and 60,000 IU since October 2014. 25OHD blood levels were 28, 81, 204, 216, 225, 166, and 218ng/ml. Subject 2 began 10,000 IU in Nov 2011, increased to 20,000 IU in Feb 2014, 25,000 IU in June 2014, and 30,000 IU in Oct 2014, and then decreased to 20,000 IU in June 2015. 25OHD blood levels were 96.6, 161.1 and 106.9ng/ml. He reported marked clinical improvement in his asthma. Subject 3 started on daily 10,000 IU in Sept 2013, increasing to 20,000 IU on Nov 2013. 25OHD blood levels were 31.4, 102, 164, 148, and 143ng/ml. No one developed hypercalcemia or any adverse events. The major finding of this case series is prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU was safely tolerated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dosimetric characteristics with spatial fractionation using electron grid therapy.

PubMed

Meigooni, A S; Parker, S A; Zheng, J; Kalbaugh, K J; Regine, W F; Mohiuddin, M

2002-01-01

Recently, promising clinical results have been shown in the delivery of palliative treatments using megavoltage photon grid therapy. However, the use of megavoltage photon grid therapy is limited in the treatment of bulky superficial lesions where critical radiosensitive anatomical structures are present beyond tumor volumes. As a result, spatially fractionated electron grid therapy was investigated in this project. Dose distributions of 1.4-cm-thick cerrobend grid blocks were experimentally determined for electron beams ranging from 6 to 20 MeV. These blocks were designed and fabricated at out institution to fit into a 20 x 20-cm(2) electron cone of a commercially available linear accelerator. Beam profiles and percentage depth dose (PDD) curves were measured in Solid Water phantom material using radiographic film, LiF TLD, and ionometric techniques. Open-field PDD curves were compared with those of single holes grid with diameters of 1.5, 2.0, 2.5, 3.0, and 3.5 cm to find the optimum diameter. A 2.5-cm hole diameter was found to be the optimal size for all electron energies between 6 and 20 MeV. The results indicate peak-to-valley ratios decrease with depth and the largest ratio is found at Dmax. Also, the TLD measurements show that the dose under the blocked regions of the grid ranged from 9.7% to 39% of the dose beneath the grid holes, depending on the measurement location and beam energy.

Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, Aaron M.; Czerminska, Maria; Jaenne, Pasi A.

2006-07-01

Purpose: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. Methods and Materials: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m{sup 2}). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patientsmore » received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. Results: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90% (range, 66-98.3%) (p = 0.20), respectively, for the patients who did not develop pneumonitis. Conclusions: Intensity-modulated RT treatment for mesothelioma after EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when standard dose parameters were used. We therefore recommend caution in the utilization of this technique. Our data suggest that with IMRT, metrics such as V5 and MLD should be considered in addition to V20 to determine tolerance levels in future patients.« less

Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.

PubMed

Krösser, S; Tillner, J; Fluck, M; Ungethüm, W; Wolna, P; Kovar, A

2007-05-01

Sarizotan is a 5-HTIA receptor agonist with high affinity for D3 and D4 receptors. Here we report the pharmacokinetic and tolerability results from four Phase 1 studies. Two single-dose (5 -25 mg, n = 25, 0.5 - 5 mg, n = 16) and two multiple-dose (10 and 20 mg b.i.d., n = 30, 5 mg b.i.d., n = 12) studies with orally administered sarizotan HCl were carried out in healthy subjects. Plasma sarizotan HCl concentrations were measured using a validated HPLC method and fluorescence or MS/MS detection. Pharmacokinetic parameters were obtained using standard non-compartmental methods. Sarizotan was rapidly absorbed, group-median times to reach maximum concentration (tmax) ranged from 0.5 -2.25 h after single doses and during steady state. Maximum plasma concentration (Cmax) and tmax were slightly dependent on formulation and food intake, whereas area under the curve (AUC) was unaffected by these factors. AUC and Cmax increased dose-proportionally over the tested dose range. Independently of dose and time, sarizotan HCl plasma concentrations declined polyexponentially with a terminal elimination half-life (t1/2) of 5 - 7 h. Accumulation factors corresponded to t1/2 values, and steady state was reached within 24 h. Plasma metabolite concentrations were considerably lower than those of the parent drug. The ratio metabolite AUC : parent drug AUC was time- and dose-independent for all three metabolites suggesting that the metabolism of sarizotan is non-saturable in the tested dose range. The pharmacokinetics of sarizotan were dose-proportional and time-independent for the dose range 0.5 -25 mg). The drug was well-tolerated by healthy subjects up to a single dose of 20 mg.

X-ray surface dose measurements using TLD extrapolation.

PubMed

Kron, T; Elliot, A; Wong, T; Showell, G; Clubb, B; Metcalfe, P

1993-01-01

Surface dose measurements in therapeutic x-ray beams are of importance in determining the dose to the skin of patients undergoing radiotherapy. Measurements were performed in the 6-MV beam of a medical linear accelerator with LiF thermoluminescence dosimeters (TLD) using a solid water phantom. TLD chips (surface area 3.17 x 3.17 cm2) of three different thicknesses (0.230, 0.099, and 0.038 g/cm2) were used to extrapolate dose readings to an infinitesimally thin layer of LiF. This surface dose was measured for field sizes ranging from 1 x 1 cm2 to 40 x 40 cm2. The surface dose relative to maximum dose was found to be 10.0% for a field size of 5 x 5 cm2, 16.3% for 10 x 10 cm2, and 26.9% for 20 x 20 cm2. Using a 6-mm Perspex block tray in the beam increased the surface dose in these fields to 10.7%, 17.7%, and 34.2% respectively. Due to the small size of the TLD chips, TLD extrapolation is applicable also for intracavity and exit dose determinations. The technique used for in vivo dosimetry could provide clinicians information about the build up of dose up to 1-mm depth in addition to an extrapolated surface dose measurement.

Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods

PubMed Central

2009-01-01

Background The International Commission on Radiological Protection (ICRP) recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model. Methods Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa) methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR) and tests against the linear model. Results The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years), liver (36.9), lung (13.6), leukaemia (23.66), and pancreas (11.86) and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose) are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range. Conclusion Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of latency and risk from 10 mSv are obtained from the 0 - 20 mSv and 5 - 500 mSv subcohorts. Large and significant cancer risks for Japanese survivors exposed to less than 20 mSv external radiation from the atomic bombs in 1945 cast doubt on the ICRP recommended annual occupational dose limit. PMID:20003238

Cumulative doses analysis in young trauma patients: a single-centre experience.

PubMed

Salerno, Sergio; Marrale, Maurizio; Geraci, Claudia; Caruso, Giuseppe; Lo Re, Giuseppe; Lo Casto, Antonio; Midiri, Massimo

2016-02-01

Multidetector computed tomography (MDCT) represents the main source of radiation exposure in trauma patients. The radiation exposure of young patients is a matter of considerable medical concern due to possible long-term effects. Multiple MDCT studies have been observed in the young trauma population with an increase in radiation exposure. We have identified 249 young adult patients (178 men and 71 women; age range 14-40 years) who had received more than one MDCT study between June 2010 and June 2014. According to the International Commission on Radiological Protection publication, we have calculated the cumulative organ dose tissue-weighting factors by using CT-EXPO software(®). We have observed a mean cumulative dose of about 27 mSv (range from 3 to 297 mSv). The distribution analysis is characterised by low effective dose, below 20 mSv, in the majority of the patients. However, in 29 patients, the effective dose was found to be higher than 20 mSv. Dose distribution for the various organs analysed (breasts, ovaries, testicles, heart and eye lenses) shows an intense peak for lower doses, but in some cases high doses were recorded. Even though cumulative doses may have long-term effects, which are still under debate, high doses are observed in this specific group of young patients.

Bioavailability and Preliminary Clinical Efficacy of Intrarectal Artesunate in Ghanaian Children with Moderate Malaria

PubMed Central

Krishna, Sanjeev; Planche, Tim; Agbenyega, Tsiri; Woodrow, Charles; Agranoff, Dan; Bedu-Addo, George; Owusu-Ofori, Alex K.; Appiah, John Adabie; Ramanathan, Surash; Mansor, Sharif M.; Navaratnam, Visweswaran

2001-01-01

We report the first detailed pharmacokinetic assessment of intrarectal (i.r.) artesunate (ARS) in African children. Artesunate was given intravenously (i.v.; 2.4 mg/kg of body weight) and i.r. (10 or 20 mg/kg formulated as 50- or 200-mg suppositories [Rectocaps]) in a crossover study design to 34 Ghanaian children with moderate falciparum malaria. The median relative bioavailability of dihydroartemisinin (DHA), the active antimalarial metabolite of ARS, was higher in the low-dose i.r. group (10 mg/kg) than in the high-dose i.r. group (20 mg/kg) (58 versus 23%; P = 0.018). There was wide interpatient variation in the area under the concentration-time curve after i.r. ARS administration (up to 9-fold in the high-dose group and 20-fold in the low-dose group). i.r. administered ARS was more rapidly absorbed in the low-dose group than the high-dose group (median [range] absorption half-lives, 0.7 h [0.3 to 1.24 h] versus 1.1 h [0.6 to 2.7 h] [P = 0.023]. i.r. administered ARS was eliminated with a median (range) half-life of 0.8 h (0.4 to 2.7 h) (low-dose group and 0.9 h (0.1 to 2.5 h) (high-dose group) (P = 1). The fractional clearances of DHA were 3.9, 2.6, and 1.5 liters/kg/h for the 20-mg/kg, 10-mg/kg and i.v. groups, respectively (P = 0.001 and P = 0.06 for the high-and low-dose i.r. groups compared with the i.v. groups, respectively). The median volumes of distribution for DHA were 1.5 liters kg (20 mg/kg, i.r. group), 1.8 liters/kg (10 mg/kg, i.r. group), and 0.6 liters/kg (i.v. group) (P < 0.05 for both i.r. groups compared with the i.v. group). Parasite clearance kinetics were comparable in all treatment groups. i.r. administered ARS may be a useful alternative to parenterally administered ARS in the management of moderate childhood malaria and should be studied further. PMID:11158748

Combined photon-electron beams in the treatment of the supraclavicular lymph nodes in breast cancer: A novel technique that achieves adequate coverage while reducing lung dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salem, Ahmed, E-mail: ahmed.salem@doctors.org.uk; Mohamad, Issa; Dayyat, Abdulmajeed

2015-10-01

Radiation pneumonitis is a well-documented side effect of radiation therapy for breast cancer. The purpose of this study was to compare combined photon-electron, photon-only, and electron-only plans in the radiation treatment of the supraclavicular lymph nodes. In total, 13 patients requiring chest wall and supraclavicular nodal irradiation were planned retrospectively using combined photon-electron, photon-only, and electron-only supraclavicular beams. A dose of 50 Gy over 25 fractions was prescribed. Chest wall irradiation parameters were fixed for all plans. The goal of this planning effort was to cover 95% of the supraclavicular clinical target volume (CTV) with 95% of the prescribed dosemore » and to minimize the volume receiving ≥ 105% of the dose. Comparative end points were supraclavicular CTV coverage (volume covered by the 95% isodose line), hotspot volume, maximum radiation dose, contralateral breast dose, mean total lung dose, total lung volume percentage receiving at least 20 Gy (V{sub 20} {sub Gy}), heart volume percentage receiving at least 25 Gy (V{sub 25} {sub Gy}). Electron and photon energies ranged from 8 to 18 MeV and 4 to 6 MV, respectively. The ratio of photon-to-electron fractions in combined beams ranged from 5:20 to 15:10. Supraclavicular nodal coverage was highest in photon-only (mean = 96.2 ± 3.5%) followed closely by combined photon-electron (mean = 94.2 ± 2.5%) and lowest in electron-only plans (mean = 81.7 ± 14.8%, p < 0.001). The volume of tissue receiving ≥ 105% of the prescription dose was higher in the electron-only (mean = 69.7 ± 56.1 cm{sup 3}) as opposed to combined photon-electron (mean = 50.8 ± 40.9 cm{sup 3}) and photon-only beams (mean = 32.2 ± 28.1 cm{sup 3}, p = 0.114). Heart V{sub 25} {sub Gy} was not statistically different among the plans (p = 0.999). Total lung V{sub 20} {sub Gy} was lowest in electron-only (mean = 10.9 ± 2.3%) followed by combined photon-electron (mean = 13.8 ± 2.3%) and highest in photon-only plans (mean = 16.2 ± 3%, p < 0.001). As expected, photon-only plans demonstrated the highest target coverage and total lung V{sub 20} {sub Gy}. The superiority of electron-only beams, in terms of decreasing lung dose, is set back by the dosimetric hotspots associated with such plans. Combined photon-electron treatment is a feasible technique for supraclavicular nodal irradiation and results in adequate target coverage, acceptable dosimetric hotspot volume, and slightly reduced lung dose.« less

Impact of field number and beam angle on functional image-guided lung cancer radiotherapy planning

NASA Astrophysics Data System (ADS)

Tahir, Bilal A.; Bragg, Chris M.; Wild, Jim M.; Swinscoe, James A.; Lawless, Sarah E.; Hart, Kerry A.; Hatton, Matthew Q.; Ireland, Rob H.

2017-09-01

To investigate the effect of beam angles and field number on functionally-guided intensity modulated radiotherapy (IMRT) normal lung avoidance treatment plans that incorporate hyperpolarised helium-3 magnetic resonance imaging (3He MRI) ventilation data. Eight non-small cell lung cancer patients had pre-treatment 3He MRI that was registered to inspiration breath-hold radiotherapy planning computed tomography. IMRT plans that minimised the volume of total lung receiving  ⩾20 Gy (V20) were compared with plans that minimised 3He MRI defined functional lung receiving  ⩾20 Gy (fV20). Coplanar IMRT plans using 5-field manually optimised beam angles and 9-field equidistant plans were also evaluated. For each pair of plans, the Wilcoxon signed ranks test was used to compare fV20 and the percentage of planning target volume (PTV) receiving 90% of the prescription dose (PTV90). Incorporation of 3He MRI led to median reductions in fV20 of 1.3% (range: 0.2-9.3% p  =  0.04) and 0.2% (range: 0 to 4.1%; p  =  0.012) for 5- and 9-field arrangements, respectively. There was no clinically significant difference in target coverage. Functionally-guided IMRT plans incorporating hyperpolarised 3He MRI information can reduce the dose received by ventilated lung without comprising PTV coverage. The effect was greater for optimised beam angles rather than uniformly spaced fields.

Intraarticular Sacroiliac Joint Injection Under Computed Tomography Fluoroscopic Guidance: A Technical Note to Reduce Procedural Time and Radiation Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paik, Nam Chull, E-mail: pncspine@gmail.com

2016-07-15

PurposeA technique for computed tomography fluoroscopy (CTF)-guided intraarticular (IA) sacroiliac joint (SIJ) injection was devised to limit procedural time and radiation dose.MethodsOur Institutional Review Board approved this retrospective analysis and waived the requirement for informed consent. Overall, 36 consecutive diagnostic or therapeutic IA SIJ injections (unilateral, 20; bilateral, 16) performed in 34 patients (female, 18; male, 16) with a mean age of 45.5 years (range 20–76 years) under CTF guidance were analyzed, assessing technical success (i.e., IA contrast spread), procedural time, and radiation dose.ResultsAll injections were successful from a technical perspective and were free of serious complications. Respective median proceduralmore » times and effective doses of SIJ injection were as follows: unilateral, 5.28 min (range 3.58–8.00 min) and 0.11 millisievert (mSv; range 0.07–0.24 mSv); and bilateral, 6.72 min (range 4.17–21.17 min) and 0.11 mSv (range 0.09–0.51 mSv).ConclusionsGiven the high rate of technical success achieved in limited time duration and with little radiation exposure, CTF-guided IA SIJ injection is a practical and low-risk procedure.« less

Investigation of EBT2 and EBT3 films for proton dosimetry in the 4-20 MeV energy range.

PubMed

Reinhardt, S; Würl, M; Greubel, C; Humble, N; Wilkens, J J; Hillbrand, M; Mairani, A; Assmann, W; Parodi, K

2015-03-01

Radiochromic films such as Gafchromic EBT2 or EBT3 films are widely used for dose determination in radiation therapy because they offer a superior spatial resolution compared to any other digital dosimetric 2D detector array. The possibility to detect steep dose gradients is not only attractive for intensity-modulated radiation therapy with photons but also for intensity-modulated proton therapy. Their characteristic dose rate-independent response makes radiochromic films also attractive for dose determination in cell irradiation experiments using laser-driven ion accelerators, which are currently being investigated as future medical ion accelerators. However, when using these films in ion beams, the energy-dependent dose response in the vicinity of the Bragg peak has to be considered. In this work, the response of these films for low-energy protons is investigated. To allow for reproducible and background-free irradiation conditions, the films were exposed to mono-energetic protons from an electrostatic accelerator, in the 4-20 MeV energy range. For comparison, irradiation with clinical photons was also performed. It turned out that in general, EBT2 and EBT3 films show a comparable performance. For example, dose-response curves for photons and protons with energies as low as 11 MeV show almost no differences. However, corrections are required for proton energies below 11 MeV. Care has to be taken when correction factors are related to an average LET from depth-dose measurements, because only the dose-averaged LET yields similar results as obtained in mono-energetic measurements.

SU-F-T-274: Modified Dose Calibration Methods for IMRT QA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, W; Westlund, S

2016-06-15

Purpose: To investigate IMRT QA uncertainties caused by dose calibration and modify widely used dose calibration procedures to improve IMRT QA accuracy and passing rate. Methods: IMRT QA dose measurement is calibrated using a calibration factor (CF) that is the ratio between measured value and expected value corresponding to the reference fields delivered on a phantom. Two IMRT QA phantoms were used for this study: a 30×30×30 cm3 solid water cube phantom (Cube), and the PTW Octavius phantom. CF was obtained by delivering 100 MUs to the phantoms with different reference fields ranging from 3×3 cm2 to 20×20 cm{sup 2}.more » For Cube, CFs were obtained using the following beam arrangements: 2-AP Field - chamber at dmax, 2-AP Field - chamber at isocenter, 4-beam box - chamber at isocenter, and 8 equally spaced fields and chamber at isocenter. The same plans were delivered on Octavius and CFs were derived for the dose at the isocenter using the above beam arrangements. The Octavius plans were evaluated with PTW-VeriSoft (Gamma criteria of 3%/3mm). Results: Four head and neck IMRT plans were included in this study. For point dose measurement with Cube, the CFs with 4-Field gave the best agreement between measurement and calculation within 4% for large field plans. All the measurement results agreed within 2% for a small field plan. Compared with calibration field sizes, 5×5 to 15×15 were more accurate than other field sizes. For Octavius, 4-Field calibration increased passing rate by up to 10% compared to AP calibration. Passing rate also increased by up to 4% with the increase of field size from 3×3 to 20×20. Conclusion: IMRT QA results are correlated with calibration methods used. The dose calibration using 4-beam box with field sizes from 5×5 to 20×20 can improve IMRT QA accuracy and passing rate.« less

Monte Carlo evaluation of magnetically focused proton beams for radiosurgery

NASA Astrophysics Data System (ADS)

McAuley, Grant A.; Heczko, Sarah L.; Nguyen, Theodore T.; Slater, James M.; Slater, Jerry D.; Wroe, Andrew J.

2018-03-01

The purpose of this project is to investigate the advantages in dose distribution and delivery of proton beams focused by a triplet of quadrupole magnets in the context of potential radiosurgery treatments. Monte Carlo simulations were performed using various configurations of three quadrupole magnets located immediately upstream of a water phantom. Magnet parameters were selected to match what can be commercially manufactured as assemblies of rare-earth permanent magnetic materials. Focused unmodulated proton beams with a range of ~10 cm in water were target matched with passive collimated beams (the current beam delivery method for proton radiosurgery) and properties of transverse dose, depth dose and volumetric dose distributions were compared. Magnetically focused beams delivered beam spots of low eccentricity to Bragg peak depth with full widths at the 90% reference dose contour from ~2.5 to 5 mm. When focused initial beam diameters were larger than matching unfocused beams (10 of 11 cases) the focused beams showed 16%–83% larger peak-to-entrance dose ratios and 1.3 to 3.4-fold increases in dose delivery efficiency. Peak-to-entrance and efficiency benefits tended to increase with larger magnet gradients and larger initial diameter focused beams. Finally, it was observed that focusing tended to shift dose in the water phantom volume from the 80%–20% dose range to below 20% of reference dose, compared to unfocused beams. We conclude that focusing proton beams immediately upstream from tissue entry using permanent magnet assemblies can produce beams with larger peak-to-entrance dose ratios and increased dose delivery efficiencies. Such beams could potentially be used in the clinic to irradiate small-field radiosurgical targets with fewer beams, lower entrance dose and shorter treatment times.

Correlation of Radiation Dose Estimates by DIC with the METREPOL Hematological Classes of Disease Severity.

PubMed

Port, M; Pieper, B; Dörr, H D; Hübsch, A; Majewski, M; Abend, M

2018-05-01

The degree of severity of hematologic acute radiation syndrome (HARS) may vary across the range of radiation doses, such that dose alone may be a less reliable predictor of clinical course. We sought to elucidate the relationship between absorbed dose and risk of clinically relevant HARS in humans. We used the database SEARCH (System for Evaluation and Archiving of Radiation Accidents based on Case Histories), which contains the histories of radiation accident victims. From 153 cases we extracted data on dose estimates using the dicentric assay to measure individual biological dosimetry. The data were analyzed according to the corresponding hematological response categories of clinical significance (H1-4). These categories are derived from the medical treatment protocols for radiation accident victims (METREPOL) and represent the clinical outcome of HARS based on severity categories ranging from 1-4. In addition, the category H0 represents a post-exposure hematological response that is within the normal range for nonexposed individuals. Age at exposure, gender and ethnicity were considered as potential confounders in unconditional cumulative logistic regression analysis. In most cases, victims were Caucasian (82.4%) and male (92.8%), who originated from either the Chernobyl (69.3%) or Goiânia (10.5%) accident, and nearly 60% were aged 20-40 years at time of exposure. All individuals were whole-body exposed (mean 3.8 Gy, stdev ±3.1), and single exposures were predominantly reported (79%). Seventy percent of victims in category H0 were exposed to ≤1 Gy, with rapidly decreasing proportions of H0 seen at doses up to 5 Gy. There were few HARS H4 cases reported at exposed dose of 1-2 Gy, while 82% of H4 cases received doses of >5 Gy. HARS H1-3 cases varied among dose ranges from 1-5 Gy. In summary, single whole-body radiation doses <1 Gy and >5 Gy corresponded in general with H0 and H3-4, respectively, and this was consistent with medical expectations. This underlines the usefulness of dose estimates for HARS prediction. However, whole-body doses between 1-5 Gy poorly corresponded to HARS H1-3. The dose range of 1-5 Gy was of limited value for medical decision-making regarding, e.g., hospitalization for H2-3, but not H1 and treatment decisions that differ between H1-3. Also, there were some H0 cases at high doses and H2-4 cases at low doses, thereby challenging an individual recommendation based solely on dose.

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers

PubMed Central

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-01-01

Aim The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Methods Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. Results ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Conclusions Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. PMID:23016924

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

PubMed

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-05-01

The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Prospective study of direct radiation exposure measurements for family members living with patients with prostate (125)I seed implantation: Evidence of radiation safety.

PubMed

Hanada, Takashi; Yorozu, Atsunori; Shinya, Yukiko; Kuroiwa, Nobuko; Ohashi, Toshio; Saito, Shiro; Shigematsu, Naoyuki

2016-01-01

To broaden the current understanding of radiation exposure and risk and to provide concrete evidence of radiation safety related to (125)I seed implantation. Direct radiation exposure measurements were obtained from dosimeters provided to 25 patients who underwent (125)I seed implantation, along with their family members. The estimated lifetime exposure dose and the precaution time for holding children near the patient's chest were calculated in two study periods. During the first and second study period, the mean estimated lifetime exposure doses were, respectively, 7.61 (range: 0.45, 20.21) mSv and 6.84 (range: 0.41, 19.20) mSv for patients, and 0.19 (range: 0.02, 0.54) mSv and 0.25 (range: 0.04, 1.00) mSv for family members. The mean ratios of first and second period measurements were 1.05 (range: 0.44, 3.18) for patients and 1.82 (range: 0.21, 7.04) for family members. The corresponding absolute differences between first and second period measurements were -0.77 (range: -11.40, 7.63) mSv and 0.06 (range: -0.26, 0.79) mSv, respectively. Assuming a dose limit of 1 mSv, the precaution times for holding a child every day of the first and second periods were 250.9 (range: 71.3, 849.4) min and 275.2 (range: 75.0, 883.4) min, respectively. Assuming a dose limit of 0.5 mSv, the corresponding precaution times were 179.0 (range: 35.6, 811.5) min and 178.9 (range: 37.5, 1131.8) min, respectively. Our study demonstrated low radiation exposures to family members of patients undergoing (125)I prostate implantation. It was clear that (125)I seed implantation did not pose a threat to the safety of family members. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Tumor Control Outcomes Following Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases from Renal Cell Carcinoma

PubMed Central

Zelefsky, Michael J; Greco, Carlo; Motzer, Robert; Magsanoc, Juan Martin; Pei, Xin; Lovelock, Michael; Mechalakos, Jim; Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya

2014-01-01

Purpose To report tumor local progression-free outcomes following treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Methods and Materials Between 2004 and 2010, a total of 105 lesions from renal cell carcinomas were treated with either SD-IGRT to prescription doses of 18–24 Gy (median, 24 Gy) or hypofractionation (3 or 5 fractions) with prescription doses ranging between 20 and 30 Gy. The median follow-up was 12 months (range, 1–48 months). Results The overall 3-year actuarial local progression-free survival (LPFS) for all lesions was 44%. The 3-year LPFS for those who received high single-dose (24 Gy; n = 45), low single-dose (< 24 Gy; n = 14), and hypofractionation regimens (n = 46) were 88%, 21%, and 17%, respectively (high single dose versus low single dose, p = 0.001; high single dose versus hypofractionation, p < 0.001). Multivariate analysis revealed the following variables as significant predictors of improved LPFS: dose of 24 Gy compared with lower dose (p = 0.009), and single dose versus hypofractionation (p = 0.008). Conclusion High-dose SD-IGRT is a non-invasive procedure resulting in high probability of local tumor control for metastatic renal cell cancers, generally considered radioresistant according to classical radiobiological ranking. PMID:21596489

SU-E-T-287: Robustness Study of Passive-Scattering Proton Therapy in Lung: Is Range and Setup Uncertainty Calculation On the Initial CT Enough to Predict the Plan Robustness?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, X; Dormer, J; Kenton, O

Purpose: Plan robustness of the passive-scattering proton therapy treatment of lung tumors has been studied previously using combined uncertainties of 3.5% in CT number and 3 mm geometric shifts. In this study, we investigate whether this method is sufficient to predict proton plan robustness by comparing to plans performed on weekly verification CT scans. Methods: Ten lung cancer patients treated with passive-scattering proton therapy were randomly selected. All plans were prescribed 6660cGy in 37 fractions. Each initial plan was calculated using +/− 3.5% range and +/− 0.3cm setup uncertainty in x, y and z directions in Eclipse TPS(Method-A). Throughout themore » treatment course, patients received weekly verification CT scans to assess the daily treatment variation(Method-B). After contours and imaging registrations are verified by the physician, the initial plan with the same beamline and compensator was mapped into the verification CT. Dose volume histograms (DVH) were evaluated for robustness study. Results: Differences are observed between method A and B in terms of iCTV coverage and lung dose. Method-A shows all the iCTV D95 are within +/− 1% difference, while 20% of cases fall outside +/−1% range in Method-B. In the worst case scenario(WCS), the iCTV D95 is reduced by 2.5%. All lung V5 and V20 are within +/−5% in Method-A while 15% of V5 and 10% of V20 fall outside of +/−5% in Method-B. In the WCS, Lung V5 increased by 15% and V20 increased by 9%. Method A and B show good agreement with regard to cord maximum and Esophagus mean dose. Conclusion: This study suggests that using range and setup uncertainty calculation (+/−3.5% and +/−3mm) may not be sufficient to predict the WCS. In the absence of regular verification scans, expanding the conventional uncertainty parameters(e.g., to +/−3.5% and +/−4mm) may be needed to better reflect plan actual robustness.« less

Dosimetric characteristics of a MOSFET dosimeter for clinical electron beams.

PubMed

Manigandan, D; Bharanidharan, G; Aruna, P; Devan, K; Elangovan, D; Patil, Vikram; Tamilarasan, R; Vasanthan, S; Ganesan, S

2009-09-01

The fundamental dosimetric characteristics of commercially available metal oxide semiconductor field effect transistor (MOSFET) detectors were studied for clinical electron beam irradiations. MOSFET showed excellent linearity against doses measured using an ion chamber in the dose range of 20-630cGy. MOSFET reproducibility is better at high doses compared to low doses. The output factors measured with the MOSFET were within +/-3% when compared with those measured with a parallel plate chamber. From 4 to 12MeV, MOSFETs showed a large angular dependence in the tilt directions and less in the axial directions. MOSFETs do not show any dose-rate dependence between 100 and 600MU/min. However, MOSFETs have shown under-response when the dose per pulse of the beam is decreased. No measurable effect in MOSFET response was observed in the temperature range of 23-40 degrees C. The energy dependence of a MOSFET dosimeter was within +/-3.0% for 6-18MeV electron beams and 5.5% for 4MeV ones. This study shows that MOSFET detectors are suitable for dosimetry of electron beams in the energy range of 4-18MeV.

Estimation of extremely small field radiation dose for brain stereotactic radiotherapy using the Vero4DRT system.

PubMed

Nakayama, Shinichi; Monzen, Hajime; Onishi, Yuichi; Kaneshige, Soichiro; Kanno, Ikuo

2018-06-01

The purpose of this study was a dosimetric validation of the Vero4DRT for brain stereotactic radiotherapy (SRT) with extremely small fields calculated by the treatment planning system (TPS) iPlan (Ver.4.5.1; algorithm XVMC). Measured and calculated data (e.g. percentage depth dose [PDD], dose profile, and point dose) were compared for small square fields of 30 × 30, 20 × 20, 10 × 10 and 5 × 5 mm 2 using ionization chambers of 0.01 or 0.04 cm 3 and a diamond detector. Dose verifications were performed using an ionization chamber and radiochromic film (EBT3; the equivalent field sizes used were 8.2, 8.7, 8.9, 9.5, and 12.9 mm 2 ) for five brain SRT cases irradiated with dynamic conformal arcs. The PDDs and dose profiles for the measured and calculated data were in good agreement for fields larger than or equal to 10 × 10 mm 2 when an appropriate detector was chosen. The dose differences for point doses in fields of 30 × 30, 20 × 20, 10 × 10 and 5 × 5 mm 2 were +0.48%, +0.56%, -0.52%, and +11.2% respectively. In the dose verifications for the brain SRT plans, the mean dose difference between the calculated and measured doses were -0.35% (range, -0.94% to +0.47%), with the average pass rates for the gamma index under the 3%/2 mm criterion being 96.71%, 93.37%, and 97.58% for coronal, sagittal, and axial planes respectively. The Vero4DRT system provides accurate delivery of radiation dose for small fields larger than or equal to 10 × 10 mm 2 . Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer.

PubMed

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony; Bowen, Stephen R

2018-04-01

Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung V RX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. In this ten-patient sample, CTV V95 decreased significantly from 99-100% for PBopt to 77-94% for MCrecalc and recovered to 99-100% for MCopt (P<10 -5 ). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10 -3 ). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =-1%) compared to MCrecalc (ΔD95 =-6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., V RX ). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10 -3 ). MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy.

Advanced proton beam dosimetry part II: Monte Carlo vs. pencil beam-based planning for lung cancer

PubMed Central

Maes, Dominic; Saini, Jatinder; Zeng, Jing; Rengan, Ramesh; Wong, Tony

2018-01-01

Background Proton pencil beam (PB) dose calculation algorithms have limited accuracy within heterogeneous tissues of lung cancer patients, which may be addressed by modern commercial Monte Carlo (MC) algorithms. We investigated clinical pencil beam scanning (PBS) dose differences between PB and MC-based treatment planning for lung cancer patients. Methods With IRB approval, a comparative dosimetric analysis between RayStation MC and PB dose engines was performed on ten patient plans. PBS gantry plans were generated using single-field optimization technique to maintain target coverage under range and setup uncertainties. Dose differences between PB-optimized (PBopt), MC-recalculated (MCrecalc), and MC-optimized (MCopt) plans were recorded for the following region-of-interest metrics: clinical target volume (CTV) V95, CTV homogeneity index (HI), total lung V20, total lung VRX (relative lung volume receiving prescribed dose or higher), and global maximum dose. The impact of PB-based and MC-based planning on robustness to systematic perturbation of range (±3% density) and setup (±3 mm isotropic) was assessed. Pairwise differences in dose parameters were evaluated through non-parametric Friedman and Wilcoxon sign-rank testing. Results In this ten-patient sample, CTV V95 decreased significantly from 99–100% for PBopt to 77–94% for MCrecalc and recovered to 99–100% for MCopt (P<10−5). The median CTV HI (D95/D5) decreased from 0.98 for PBopt to 0.91 for MCrecalc and increased to 0.95 for MCopt (P<10−3). CTV D95 robustness to range and setup errors improved under MCopt (ΔD95 =−1%) compared to MCrecalc (ΔD95 =−6%, P=0.006). No changes in lung dosimetry were observed for large volumes receiving low to intermediate doses (e.g., V20), while differences between PB-based and MC-based planning were noted for small volumes receiving high doses (e.g., VRX). Global maximum patient dose increased from 106% for PBopt to 109% for MCrecalc and 112% for MCopt (P<10−3). Conclusions MC dosimetry revealed a reduction in target dose coverage under PB-based planning that was regained under MC-based planning along with improved plan robustness. MC-based optimization and dose calculation should be integrated into clinical planning workflows of lung cancer patients receiving actively scanned proton therapy. PMID:29876310

Summary of retrospective asbestos and welding fume exposure estimates for a nuclear naval shipyard and their correlation with radiation exposure estimates.

PubMed

Zaebst, D D; Seel, E A; Yiin, J H; Nowlin, S J; Chen, P

2009-07-01

In support of a nested case-control study at a U.S. naval shipyard, the results of the reconstruction of historical exposures were summarized, and an analysis was undertaken to determine the impact of historical exposures to potential chemical confounders. The nested case-control study (N = 4388) primarily assessed the relationship between lung cancer and external ionizing radiation. Chemical confounders considered important were asbestos and welding fume (as iron oxide fume), and the chromium and nickel content of welding fume. Exposures to the potential confounders were estimated by an expert panel based on a set of quantitatively defined categories of exposure. Distributions of the estimated exposures and trends in exposures over time were examined for the study population. Scatter plots and Spearman rank correlation coefficients were used to assess the degree of association between the estimates of exposure to asbestos, welding fume, and ionizing radiation. Correlation coefficients were calculated separately for 0-, 15-, 20-, and 25-year time-lagged cumulative exposures, total radiation dose (which included medical X-ray dose) and occupational radiation dose. Exposed workers' estimated cumulative exposures to asbestos ranged from 0.01 fiber-days/cm(3) to just under 20,000 fiber-days/cm(3), with a median of 29.0 fiber-days/cm(3). Estimated cumulative exposures to welding fume ranged from 0.16 mg-days/m(3) to just over 30,000 mg-days/m(3), with a median of 603 mg-days/m(3). Spearman correlation coefficients between cumulative radiation dose and cumulative asbestos exposures ranged from 0.09 (occupational dose) to 0.47 (total radiation dose), and those between radiation and welding fume from 0.14 to 0.47. The estimates of relative risk for ionizing radiation and lung cancer were unchanged when lowest and highest estimates of asbestos and welding fume were considered. These results suggest a fairly large proportion of study population workers were exposed to asbestos and welding fume, that the absolute level of confounding exposure did not affect the risk estimates, and that weak relationships existed between monitored lifetime cumulative occupational radiation dose and asbestos or welding fume.

Safety and immunogenicity of a primary series of Sabin-IPV with and without aluminum hydroxide in infants.

PubMed

Verdijk, Pauline; Rots, Nynke Y; van Oijen, Monique G C T; Weldon, William C; Oberste, M Steven; Okayasu, Hiromasa; Sutter, Roland W; Bakker, Wilfried A M

2014-09-03

An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle-income countries in the context of the global polio eradication initiative. Safety and immunogenicity of Sabin-IPV (sIPV) was evaluated in a double-blind, randomized, controlled, dose-escalation trial in the target population. Healthy infants (n=20/group) aged 56-63 days, received a primary series of three intramuscular injections with low-, middle- or high-dose sIPV with or without aluminum hydroxide or with the conventional IPV based on wild poliovirus strains (wIPV). Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after three vaccinations. The incidence of local and systemic reactions was comparable with the wIPV. Seroconversion rates after three vaccinations were 100% for type 2 and type 3 polioviruses (both Sabin and wild strains) and 95-100% for type 1 polioviruses. Median titers were high in all groups. Titers were well above the log2(titer) correlated with protection (=3) for all groups. Median titers for Sabin-2 were 9.3 (range 6.8-11.5) in the low-dose sIPV group, 9.2 (range 6.8-10.2) in the low-dose adjuvanted sIPV group and 9.8 (range 5.5-15.0) in the wIPV group, Median titers against MEF-1 (wild poliovirus type 2) were 8.2 (range 4.8-10.8) in the low-dose sIPV group, 7.3 (range 4.5-10.2) in the low-dose adjuvanted Sabin-IPV group and 10.3 (range 8.5-17.0) in the wIPV group. For all poliovirus types the median titers increased with increasing dose levels. sIPV and sIPV adjuvanted with aluminum hydroxide were immunogenic and safe at all dose levels, and comparable with the wIPV. EudraCTnr: 2011-003792-11, NCT01709071. Copyright © 2014. Published by Elsevier Ltd.

Predictor of Severe Gastroduodenal Toxicity After Stereotactic Body Radiotherapy for Abdominopelvic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Sun Hyun; Kim, Mi-Sook, E-mail: mskim@kcch.re.kr; Cho, Chul Koo

2012-11-15

Purpose: To identify the predictors for the development of severe gastroduodenal toxicity (GDT) in patients treated with stereotactic body radiotherapy (SBRT) using 3 fractionations for abdominopelvic malignancies. Methods and Materials: From 2001 to 2011, 202 patients with abdominopelvic malignancies were treated with curative-intent SBRT. Among these patients, we retrospectively reviewed the clinical records of 40 patients with the eligibility criteria as follows: 3 fractionations, follow-up period {>=}1 year, absence of previous radiation therapy (RT) history or combination of external-beam RT and the presence of gastroduodenum (GD) that received a dose higher than 20% of prescribed dose. The median SBRT dosemore » was 45 Gy (range, 33-60 Gy) with 3 fractions. We analyzed the clinical and dosimetric parameters, including multiple dose-volume histogram endpoints: V{sub 20} (volume of GD that received 20 Gy), V{sub 25}, V{sub 30}, V{sub 35}, and D{sub max} (the maximum point dose). The grade of GDT was defined by the National Cancer Institute Common Toxicity Criteria version 4.0, and GDT {>=}grade 3 was defined as severe GDT. Results: The median time to the development of severe GDT was 6 months (range, 3-12 months). Severe GDT was found in 6 patients (15%). D{sub max} was the best dosimetric predictor for severe GDT. D{sub max} of 35 Gy and 38 Gy were respectively associated with a 5% and 10% probability of the development of severe GDT. A history of ulcer before SBRT was the best clinical predictor on univariate analysis (P=.0001). Conclusions: We suggest that D{sub max} is a valuable predictor of severe GDT after SBRT using 3 fractionations for abdominopelvic malignancies. A history of ulcer before SBRT should be carefully considered as a clinical predictor, especially in patients who receive a high dose to GD.« less

Risperidone dosing in children and adolescents with autistic disorder: a double-blind, placebo-controlled study.

PubMed

Kent, Justine M; Kushner, Stuart; Ning, Xiaoping; Karcher, Keith; Ness, Seth; Aman, Michael; Singh, Jaskaran; Hough, David

2013-08-01

Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5-17 years), received risperidone (low-dose: 0.125 mg/day [20 to <45 kg], 0.175 mg/day [>45 kg] or high-dose: 1.25 mg/day [20 to <45 kg], 1.75 mg/day [>45 kg]) or placebo. Mean baseline (range 27-29) to endpoint change in Aberrant Behavior Checklist-Irritability (primary endpoint) was significantly greater in the high-dose-(-12.4 [6.5]; p < 0.001), but not low-dose (-7.4 [8.1]; p = 0.164) group, versus placebo (-3.5 [10.7]). Clinical Global Impressions-Severity and Children's Yale-Brown Obsessive Compulsive Scale scores improved significantly only in the high-dose group, consistent with ABC-I results. Somnolence, sedation and increased appetite occurred more frequently in high-versus low-dose groups. Overall, increased appetite occurred most frequently.

Effect of chronic kidney disease on warfarin management in a pharmacist-managed anticoagulation clinic.

PubMed

Kleinow, Megan E; Garwood, Candice L; Clemente, Jennifer L; Whittaker, Peter

2011-09-01

There is growing evidence that kidney disease affects hepatically cleared drugs. Accordingly, we hypothesized that chronic kidney disease (CKD) would disrupt anticoagulation of warfarin-treated patients and thereby increase the amount of management required to maintain appropriate anticoagulation. Specifically, we anticipated that more dose manipulations (both dose changes and transient dose adjustments) and shorter times between scheduled clinic visits would be required for anticoagulation patients with CKD. To determine how CKD affected warfarin maintenance dose, anticoagulation stability, the proportion of clinic visits that necessitated a dose manipulation (either a change in the prescribed weekly dose or a transient dose adjustment), and the length of time between scheduled visits in 2 pharmacist-managed anticoagulation clinics. Our retrospective, cohort chart review investigated warfarin response in anticoagulation clinic patients. From the clinic database of patients with an international normalized ratio (INR) target range of 2.0-3.0, we matched 20 of 24 patients with CKD (estimated creatinine clearance less than 60 mL per minute) to 20 comparison group patients (estimated creatinine clearance greater than 60 mL per minute) based on parameters demonstrated to affect warfarin dose: ethnicity, gender, age, body surface area, and simvastatin use. We calculated the average weekly dose used to maintain target INR (assessment period range=116-1,408 days). To evaluate anticoagulation stability and patient management, we quantified several parameters, including the percentage of total time in therapeutic range, the proportion of clinic visits that required a dose change, and the time between scheduled visits. We compared group means using t-tests, and categorical data were compared using Fisher's exact test. Our population was predominantly female (75%) and of African ancestry (95%); average age 60 years. Patients with CKD required a 24% lower dose than the comparison group (mean [SD]=35.9 [10.7] vs. 47.0 [11.2] mg per week, P=0.003) and spent less time in therapeutic range required increased clinic management versus the comparison group, as indicated by a significantly higher proportion of clinic visits at which dose changes occurred (22% vs. 12%, P<0.001) and a decreased time between scheduled visits (mean [SD] of 16.0 [3.2] days vs. 19.7 [3.4] days, respectively, P=0.001). CKD was associated with both decreased warfarin maintenance dose and decreased anticoagulation stability which, in turn, required more frequent and intensive anticoagulation clinic management.

Anal wall sparing effect of an endorectal balloon in 3D conformal and intensity-modulated prostate radiotherapy.

PubMed

Smeenk, Robert Jan; van Lin, Emile N J Th; van Kollenburg, Peter; Kunze-Busch, Martina; Kaanders, Johannes H A M

2009-10-01

To investigate the anal wall (Awall) sparing effect of an endorectal balloon (ERB) in 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for prostate cancer. In 24 patients with localized prostate carcinoma, two planning CT-scans were performed: with and without ERB. A prostate planning target volume (PTV) was defined, and the Awall was delineated, using two different methods. Three-field and 4-field 3D-CRT plans, and IMRT plans were generated with a prescription dose of 78Gy. In 144 treatment plans, the minimum dose (D(min)), maximum dose (D(max)), and mean dose (D(mean)) to the Awall were calculated, as well as the Awall volumes exposed to doses ranging from >or=20Gy to >or=70Gy (V(20)-V(70), respectively). In the 3D-CRT plans, an ERB significantly reduced D(mean), D(max), and V(30)-V(70). For IMRT all investigated dose parameters were significantly reduced by the ERB. The absolute reduction of D(mean) was 12Gy in 3D-CRT and was 7.5Gy in IMRT for both methods of Awall delineation. Application of an ERB showed a significant Awall sparing effect in both 3D-CRT and IMRT. This may lead to reduced late anal toxicity in prostate radiotherapy.

Radiation dose and magnification in pelvic X-ray: EOS™ imaging system versus plain radiographs.

PubMed

Chiron, P; Demoulin, L; Wytrykowski, K; Cavaignac, E; Reina, N; Murgier, J

2017-12-01

In plain pelvic X-ray, magnification makes measurement unreliable. The EOS™ (EOS Imaging, Paris France) imaging system is reputed to reproduce patient anatomy exactly, with a lower radiation dose. This, however, has not been assessed according to patient weight, although both magnification and irradiation are known to vary with weight. We therefore conducted a prospective comparative study, to compare: (1) image magnification and (2) radiation dose between the EOS imaging system and plain X-ray. The EOS imaging system reproduces patient anatomy exactly, regardless of weight, unlike plain X-ray. A single-center comparative study of plain pelvic X-ray and 2D EOS radiography was performed in 183 patients: 186 arthroplasties; 104 male, 81 female; mean age 61.3±13.7years (range, 24-87years). Magnification and radiation dose (dose-area product [DAP]) were compared between the two systems in 186 hips in patients with a mean body-mass index (BMI) of 27.1±5.3kg/m 2 (range, 17.6-42.3kg/m 2 ), including 7 with morbid obesity. Mean magnification was zero using the EOS system, regardless of patient weight, compared to 1.15±0.05 (range, 1-1.32) on plain X-ray (P<10 -5 ). In patients with BMI<25, mean magnification on plain X-ray was 1.15±0.05 (range, 1-1.25) and, in patients with morbid obesity, 1.22±0.06 (range, 1.18-1.32). The mean radiation dose was 8.19±2.63dGy/cm 2 (range, 1.77-14.24) with the EOS system, versus 19.38±12.37dGy/cm 2 (range, 4.77-81.75) with plain X-ray (P<10 -4 ). For BMI >40, mean radiation dose was 9.36±2.57dGy/cm 2 (range, 7.4-14.2) with the EOS system, versus 44.76±22.21 (range, 25.2-81.7) with plain X-ray. Radiation dose increased by 0.20dGy with each extra BMI point for the EOS system, versus 0.74dGy for plain X-ray. Magnification did not vary with patient weight using the EOS system, unlike plain X-ray, and radiation dose was 2.5-fold lower. 3, prospective case-control study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Involvement of Resveratrol and ω-3 Polyunsaturated Fatty Acids on Sirtuin 1 Gene Expression in THP1 Cells.

PubMed

Tsuchiya, Takafumi; Endo, Ayano; Tsujikado, Kyoko; Inukai, Toshihiko

2017-10-01

Resveratrol, a kind of polyphenol, has the potential to activate the longevity gene in several cells, in the same manner as calorie restriction. We investigated the effect of resveratrol and ω-3-line polyunsaturated fatty acid on surtuin 1 (SIRT1) gene expression in human monocytes (THP1) cells. We examined the gene expression of THP1 cells using real-time polymerase chain reaction and Western blotting analysis. Resveratol, eicosapentaenoic acid (EPA) and docosahexaeanoic acid (DHA) as n-3 polyunsaturated fatty acid were added on THP1 cells. We observed the changes in the SIRT1 gene expression in those cells, under various doses of agents and in time courses. Then, we examined the interaction of glucose and mannitol on those agents׳ effect of the gene expression. The concentration range of glucose and mannitol was from 5-20mM, respectively. The SIRT1 gene expression could be defined in 24 and 48 hours both in real-time polymerase chain reaction analysis and in Western blotting. Resveratrol showed SIRT1 gene expression in a dose-dependent manner in the range of 0-20μM in both analyses. Although EPA at 10μM showed marked increase in SIRT1 gene expression compared to control condition in Western blotting, this phenomenon was not in dose-dependent manner. DHA did not exhibit any augmentation of SIRT1 gene expression in a dose-dependent manner in the range of 0-20μM in both analyses. We refined the dose-dependent inhibition of the SIRT1 gene expression within 20mM glucose medium. Although 20mM did not exhibit any inhibition, 10μM resveratrol induced the gene expression compared to control medium. Both 5 and 15mM mannitol medium did not significantly alter basic gene expression and 10μM resveratrol-induced gene expression. The present results suggest that resveratrol and EPA, but not DHA, markedly activated the SIRT1 gene expression in THP1 cells, and that high glucose medium could inhibit the basic gene expression, but not powerful resveratrol-induced gene expression, in those cells. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Optimization of Methylphenidate Extended-Release Chewable Tablet Dose in Children with ADHD: Open-Label Dose Optimization in a Laboratory Classroom Study.

PubMed

Wigal, Sharon B; Childress, Ann; Berry, Sally A; Belden, Heidi W; Chappell, Phillip; Wajsbrot, Dalia B; Nagraj, Praneeta; Abbas, Richat; Palumbo, Donna

2018-06-01

To examine methylphenidate extended-release chewable tablets (MPH ERCT) dose patterns, attention-deficit/hyperactivity disorder (ADHD) symptom scores, and safety during the 6-week, open-label (OL) dose-optimization period of a phase 3, laboratory classroom study. Boys and girls (6-12 years) diagnosed with ADHD were enrolled. MPH ERCT was initiated at 20 mg/day; participants were titrated in 10-20 mg/day increments weekly based on efficacy and tolerability (maximum dose, 60 mg/day). Dose-optimization period efficacy assessments included the ADHD Rating Scale (ADHD-RS-IV), analyzed by week in a post hoc analysis using a mixed-effects model for repeated measures with final optimized dose (20, 30/40, or 50/60 mg), visit, final optimized dose and visit interaction, and baseline score as terms. Adverse events (AEs) and concomitant medications were collected throughout the study. Mean MPH ERCT daily dose increased weekly from 29.4 mg/day after the first dose adjustment at week 1 (n = 90) to 42.8 mg/day after the final adjustment at week 5 (n = 86). Final optimized MPH ERCT dose ranged from 20 to 60 mg/day. Mean final optimized MPH ERCT dose ranged from 40.0 mg/day in 6-8 year-old participants to 44.8 mg/day for 11-12 year-old participants. There was a progressive decrease in mean (standard deviation) ADHD-RS-IV total score from 40.1 (8.72) at baseline to 12.4 (7.88) at OL week 5, with similar improvement patterns for hyperactivity/impulsivity and inattentiveness subscale scores. Participants optimized to MPH ERCT 50/60 mg/day had a significantly higher mean (standard error) ADHD-RS-IV score at baseline compared with participants optimized to MPH ERCT 20 mg/day (42.4 [1.34] vs. 35.1 [2.55]; p = 0.013). Treatment-emergent AEs were reported by 65/90 (72.2%) participants in the dose-optimization period. Dose-optimization period results describing relationships between change in ADHD symptom scores and final optimized MPH ERCT dose will be valuable for clinicians optimizing MPH ERCT dose.

Verification of Pharmacogenetics-Based Warfarin Dosing Algorithms in Han-Chinese Patients Undertaking Mechanic Heart Valve Replacement

PubMed Central

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

Objective To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. Methods We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. Results A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88–4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. Conclusions All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement. PMID:24728385

Verification of pharmacogenetics-based warfarin dosing algorithms in Han-Chinese patients undertaking mechanic heart valve replacement.

PubMed

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88-4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement.

Auditing the Immunization Data Quality from Routine Reports in Shangyu District, East China

PubMed Central

Hu, Yu; Zhang, Xinpei; Li, Qian; Chen, Yaping

2016-01-01

Objective: To evaluate the immunization data quality in Shangyu District, East China. Methods: An audit for immunization data for the year 2014 was conducted in 20 vaccination clinics of Shangyu District. The consistency of immunization data was estimated by verification factors (VFs), which was the proportion of vaccine doses reported as being administered that could be verified by written documentation at vaccination clinics. The quality of monitoring systems was evaluated using the quality index (QI). Results: The VFs of 20 vaccine doses ranged from 0.94 to 1.04 at the district level. The VFs for the 20 vaccination clinics ranged from 0.57 to 1.07. The VFs for Shangyu District was 0.98. The mean of total QI score of the 20 vaccination clinics was 80.32%. A significant correlation between the VFs of the 3rd dose of the diphtheria–tetanus–pertussis combined vaccine (DTP) and QI scores was observed at the vaccination clinic level. Conclusions: Deficiencies in data consistency and immunization reporting practice in Shangyu District were observed. Targeted measures are suggested to improve the quality of the immunization reporting system in vaccination clinics with poor data consistency. PMID:27869729

Auditing the Immunization Data Quality from Routine Reports in Shangyu District, East China.

PubMed

Hu, Yu; Zhang, Xinpei; Li, Qian; Chen, Yaping

2016-11-18

Objective: To evaluate the immunization data quality in Shangyu District, East China. Methods: An audit for immunization data for the year 2014 was conducted in 20 vaccination clinics of Shangyu District. The consistency of immunization data was estimated by verification factors (VFs), which was the proportion of vaccine doses reported as being administered that could be verified by written documentation at vaccination clinics. The quality of monitoring systems was evaluated using the quality index (QI). Results: The VFs of 20 vaccine doses ranged from 0.94 to 1.04 at the district level. The VFs for the 20 vaccination clinics ranged from 0.57 to 1.07. The VFs for Shangyu District was 0.98. The mean of total QI score of the 20 vaccination clinics was 80.32%. A significant correlation between the VFs of the 3rd dose of the diphtheria-tetanus-pertussis combined vaccine (DTP) and QI scores was observed at the vaccination clinic level. Conclusions: Deficiencies in data consistency and immunization reporting practice in Shangyu District were observed. Targeted measures are suggested to improve the quality of the immunization reporting system in vaccination clinics with poor data consistency.

Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women.

PubMed

McKeand, William

2017-09-01

Bazedoxifene is a selective estrogen receptor modulator that has estrogen agonist effects on bone and lipid metabolism while having neutral or estrogen antagonist effects on the breast and endometrium. The present report describes findings from 3 Phase I clinical studies that evaluated the single-dose pharmacokinetics (study 1; n = 84), multiple-dose pharmacokinetics (study 2; n = 23), and absolute bioavailability (study 3; n = 18) of bazedoxifene. All 3 studies enrolled healthy postmenopausal women who were either naturally postmenopausal or had undergone bilateral oophorectomy at least 6 months before the start of the study. Study 1 showed that unconjugated and total (unconjugated and conjugated) bazedoxifene levels increased proportionally with ascending oral doses of bazedoxifene (through the dose range of 5-120 mg). Evaluation with or without food intake was conducted at the 10-mg dose, with no clinically relevant effect on pharmacokinetic parameters. Study 2 showed that bazedoxifene achieved steady state in 1 week and exhibited linear pharmacokinetics in doses of 5 to 40 mg with no unexpected accumulation over the dose range. In accordance with a linear pharmacokinetic profile, mean maximum plasma concentration values increased with increasing dose, with values of 1.6, 6.2, and 12.5 ng/mL for the 5-, 20-, and 40-mg doses, respectively. In study 3, tablet and capsule formulations of bazedoxifene formulations had an estimated oral bioavailability of ~6%. The clearance of bazedoxifene was 0.4 (0.1) L/h/kg based on intravenous administration. The oral formulations had comparable exposure profiles with respect to AUC and AUC0-t, and the 90% CIs for these values were within the bioequivalence limits of 80% to 125%. Bazedoxifene was safe and well tolerated in all 3 studies. These pharmacokinetic evaluations in healthy postmenopausal women found that bazedoxifene displayed linear pharmacokinetics with doses ranging from 5 to 40 mg, with no unexpected accumulation. Food did not seem to have any clinically relevant impact on pharmacokinetic parameters. Bazedoxifene had an estimated oral bioavailability of ~6% and was safe and well tolerated in the range of doses evaluated. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma

PubMed Central

Kahl, Brad S.; Leonard, John P.; Furman, Richard R.; Brown, Jennifer R.; Byrd, John C.; Wagner-Johnston, Nina D.; Coutre, Steve E.; Benson, Don M.; Peterman, Sissy; Cho, Yoonjin; Webb, Heather K.; Johnson, David M.; Yu, Albert S.; Ulrich, Roger G.; Godfrey, Wayne R.; Miller, Langdon L.; Spurgeon, Stephen E.

2014-01-01

Idelalisib (GS-1101, CAL-101), an oral inhibitor of phosphatidylinositol 3-kinase-δ, was evaluated in a phase I study in 64 patients with relapsed indolent non-Hodgkin lymphoma (iNHL). Patients had a median (range) age of 64 (32-91) years, 34 (53%) had bulky disease (≥1 lymph nodes ≥5 cm), and 37 (58%) had refractory disease. Patients had received a median (range) of 4 (1-10) prior therapies. Eight dose regimens of idelalisib were evaluated; idelalisib was taken once or twice daily continuously at doses ranging from 50 to 350 mg. After 48 weeks, patients still benefitting (n = 19; 30%) enrolled into an extension study. Adverse events (AEs) occurring in 20% or more patients (total%/grade ≥3%) included diarrhea (36/8), fatigue (36/3), nausea (25/3), rash (25/3), pyrexia (20/3), and chills (20/0). Laboratory abnormalities included neutropenia (44/23), anemia (31/5), thrombocytopenia (25/11), and serum transaminase elevations (48/25). Twelve (19%) patients discontinued therapy due to AEs. Idelalisib induced disease regression in 46/54 (85%) of evaluable patients achieving an overall response rate of 30/64 (47%), with 1 patient having a complete response (1.6%). Median duration of response was 18.4 months, median progression-free survival was 7.6 months. Idelalisib is well tolerated and active in heavily pretreated, relapsed/refractory patients with iNHL. These trials were registered at clinicaltrials.gov as NCT00710528 and NCT01090414. PMID:24615776

Is there a place for brachytherapy in the salvage treatment of cervical lymph node metastases of head and neck cancers?

PubMed

Bartochowska, Anna; Skowronek, Janusz; Wierzbicka, Malgorzata; Leszczynska, Malgorzata; Szyfter, Witold

2015-01-01

Therapeutic options are limited for unresectable isolated cervical lymph node recurrences. The purpose of the study was to evaluate the feasibility, safety, and efficacy of high-dose-rate (HDR) and pulsed-dose-rate (PDR) brachytherapy (BT) in such cases. Sixty patients have been analyzed. All them had previously been treated with radical radiotherapy or chemoradiotherapy with or without surgery. PDR-BT and HDR-BT were used in 49 and 11 patients, respectively. In PDR-BT, a dose per pulse of 0.6-0.8 Gy (median 0.7 Gy) was given up to a median total dose of 20 Gy (range, 20-40 Gy). HDR-BT delivered a median total dose of 24 Gy (range, 7-60 Gy) in 3-10 fractions at 3-6 Gy per fraction. The overall survival and lymph node control rates at 1 and 2 years were estimated for 31.7% and 19%, and 41.4% and 27.3%, respectively. Serious late side effects (soft tissue necrosis) were observed in 11.7% of patients. Adverse events occurred statistically more often in patients >59 years (p = 0.02). HDR-BT and PDR-BT are feasible in previously irradiated patients with isolated regional lymph node metastases of head and neck cancers. The techniques should be considered if surgery is contraindicated. They provide acceptable toxicity and better tumor control than chemotherapy alone. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Spectral calibration of EBT3 and HD-V2 radiochromic film response at high dose using 20 MeV proton beams

NASA Astrophysics Data System (ADS)

Feng, Yiwei; Tiedje, Henry F.; Gagnon, Katherine; Fedosejevs, Robert

2018-04-01

Radiochromic film is used extensively in many medical, industrial, and scientific applications. In particular, the film is used in analysis of proton generation and in high intensity laser-plasma experiments where very high dose levels can be obtained. The present study reports calibration of the dose response of Gafchromic EBT3 and HD-V2 radiochromic films up to high exposure densities. A 2D scanning confocal densitometer system is employed to carry out accurate optical density measurements up to optical density 5 on the exposed films at the peak spectral absorption wavelengths. Various wavelengths from 400 to 740 nm are also scanned to extend the practical dose range of such films by measuring the response at wavelengths removed from the peak response wavelengths. Calibration curves for the optical density versus exposure dose are determined and can be used for quantitative evaluation of measured doses based on the measured optical densities. It was found that blue and UV wavelengths allowed the largest dynamic range though at some trade-off with overall accuracy.

Assessment of monitor unit limiting strategy using volumetric modulated arc therapy for cancer of hypopharynx.

PubMed

Ahamed, Shabbir; Singh, Navin; Gudipudi, Deleep; Mulinti, Suneetha; Talluri, Anil; Soubhagya, Bhudevi; Sresty, Madhusudhana

2017-03-01

To quantify relative merit of MU deprived plans against freely optimized plans in terms of plan quality and report changes induced by progressive resolution optimizer algorithm (PRO3) to the dynamic parameters of RapidArc. Ten cases of carcinoma hypopharynx were retrospectively planned in three phases without using MU tool. Replicas of these baseline plans were reoptimized using "Intermediate dose" feature and "MU tool" to reduce MUs by 20%, 35%, and 50%. Overall quality indices for target and OAR, integral dose, dose-volume spread were assessed. All plans were appraised for changes induced in RapidArc dynamic parameters and pre-treatment quality assurance (QA). With increasing MU reduction strength (MURS), MU/Gy values reduced, for all phases with an overall range of 8.6-34.7%; mean dose rate decreased among plans of each phase, phase3 plans recorded greater reductions. MURS20% showed good trade-off between MUs and plan quality. Dose-volume spread below 5Gy was higher for baseline plans while lower between 20 and 35Gy. Integral dose was lower for MURS0%, not exceeding 1.0%, compared against restrained plans. Mean leaf aperture and control point areas increased systematically, correlated negatively with increasing MURS. Absolute delta dose rate variations were least for MURS0%. MU deprived plans exhibited GAI (>93%), better than MURS0% plans. Baseline plans are superior to MU restrained plans. However, MURS20% offers equivalent and acceptable plan quality with mileage of MUs, improved GAI for complex cases. MU tool may be adopted to tailor treatment plans using PRO3. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Internal dose assessment of 210Po using biokinetic modeling and urinary excretion measurement.

PubMed

Li, Wei Bo; Gerstmann, Udo; Giussani, Augusto; Oeh, Uwe; Paretzke, Herwig G

2008-02-01

The mysterious death of Mr. Alexander Litvinenko who was most possibly poisoned by Polonium-210 ((210)Po) in November 2006 in London attracted the attention of the public to the kinetics, dosimetry and the risk of this high radiotoxic isotope in the human body. In the present paper, the urinary excretion of seven persons who were possibly exposed to traces of (210)Po was monitored. The values measured in the GSF Radioanalytical Laboratory are in the range of natural background concentration. To assess the effective dose received by those persons, the time-dependence of the organ equivalent dose and the effective dose after acute ingestion and inhalation of (210)Po were calculated using the biokinetic model for polonium (Po) recommended by the International Commission on Radiological Protection (ICRP) and the one recently published by Leggett and Eckerman (L&E). The daily urinary excretion to effective dose conversion factors for ingestion and inhalation were evaluated based on the ICRP and L&E models for members of the public. The ingestion (inhalation) effective dose per unit intake integrated over one day is 1.7 x 10(-8) (1.4 x 10(-7)) Sv Bq(-1), 2.0 x 10(-7) (9.6 x 10(-7)) Sv Bq(-1) over 10 days, 5.2 x 10(-7) (2.0 x 10(-6)) Sv Bq(-1) over 30 days and 1.0 x 10(-6) (3.0 x 10(-6)) Sv Bq(-1) over 100 days. The daily urinary excretions after acute ingestion (inhalation) of 1 Bq of (210)Po are 1.1 x 10(-3) (1.0 x 10(-4)) on day 1, 2.0 x 10(-3) (1.9 x 10(-4)) on day 10, 1.3 x 10(-3) (1.7 x 10(-4)) on day 30 and 3.6 x 10(-4) (8.3 x 10(-5)) Bq d(-1) on day 100, respectively. The resulting committed effective doses range from 2.1 x 10(-3) to 1.7 x 10(-2) mSv by an assumption of ingestion and from 5.5 x 10(-2) to 4.5 x 10(-1) mSv by inhalation. For the case of Mr. Litvinenko, the mean organ absorbed dose as a function of time was calculated using both the above stated models. The red bone marrow, the kidneys and the liver were considered as the critical organs. Assuming a value of lethal absorbed dose of 5 Gy to the bone marrow, 6 Gy to the kidneys and 8 Gy to the liver, the amount of (210)Po which Mr. Litvinenko might have ingested is therefore estimated to range from 27 to 1,408 MBq, i.e 0.2-8.5 microg, depending on the modality of intake and on different assumptions about blood absorption.

Vigabatrin pediatric dosing information for refractory complex partial seizures: results from a population dose-response analysis.

PubMed

Nielsen, Jace C; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G; Wesche, David L

2014-12-01

We predicted vigabatrin dosages for adjunctive therapy for pediatric patients with refractory complex partial seizures (rCPS) that would produce efficacy comparable to that observed for approved adult dosages. A dose-response model related seizure-count data to vigabatrin dosage to identify dosages for pediatric rCPS patients. Seizure-count data were obtained from three pediatric and two adult rCPS clinical trials. Dosages were predicted for oral solution and tablet formulations. Predicted oral solution dosages to achieve efficacy comparable to that of a 1 g/day adult dosage were 350 and 450 mg/day for patients with body weight ranges 10-15 and >15-20 kg, respectively. Predicted oral solution dosages for efficacy comparable to a 3 g/day adult dosage were 1,050 and 1,300 mg/day for weight ranges 10-15 and >15-20 kg, respectively. Predicted tablet dosage for efficacy comparable to a 1 g/day adult dosage was 500 mg/day for weight ranges 25-60 kg. Predicted tablet dosage for efficacy comparable to a 3 g/day adult dosage was 2,000 mg for weight ranges 25-60 kg. Vigabatrin dosages were identified for pediatric rCPS patients with body weights ≥10 kg. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Efficacy and safety of ascending doses of praziquantel against Schistosoma haematobium infection in preschool-aged and school-aged children: a single-blind randomised controlled trial.

PubMed

Coulibaly, Jean T; Panic, Gordana; Yapi, Richard B; Kovač, Jana; Barda, Beatrice; N'Gbesso, Yves K; Hattendorf, Jan; Keiser, Jennifer

2018-06-01

Despite decades of experience with praziquantel treatment in school-aged children (SAC) and adults, we still face considerable knowledge gaps relevant to the successful treatment of preschool-aged children (PSAC). This study aimed to assess the efficacy and safety of escalating praziquantel dosages in PSAC infected with Schistosoma haematobium. We conducted a randomised, dose-finding trial in PSAC (2-5 years) and as comparator a cohort of SAC (6-15 years) infected with S. haematobium in Côte d'Ivoire. A total of 186 PSAC and 195 SAC were randomly assigned to 20, 40 or 60 mg/kg praziquantel or placebo. The nature of the dose-response relationship in terms of cure rate (CR) was the primary objective. Egg reduction rate (ERR) and tolerability were secondary outcomes. CRs and ERRs were assessed using triplicate urine filtration over 3 consecutive days. Available-case analysis was performed including all participants with primary endpoint data. A total of 170 PSAC and 174 SAC received treatment. Almost 90% of PSAC and three quarters of SAC were lightly infected with S. haematobium. Follow-up data were available for 157 PSAC and 166 SAC. In PSAC, CRs of praziquantel were 85.7% (30/35), 78.0% (32/41) and 68.3% (28/41) at 20, 40 and 60 mg/kg and 47.5% (19/40) for placebo. In SAC, CRs were 10.8% for placebo (4/37), 55.6% for 20 mg/kg (25/45), 68.3% for 40 mg/kg (28/41) and 60.5% for 60 mg/kg (26/43). ERRs based on geometric means ranged between 96.5% (60 mg/kg) and 98.3% (20 mg/kg) in PSAC and between 97.6% (20 mg/kg and 60 mg/kg) and 98.6% (40 mg/kg) in SAC. Adverse events were mild and transient. Praziquantel revealed dose-independent efficacy against light infections of S. haematobium. Over the dose range tested, praziquantel displayed a ceiling effect with the highest response for 20 mg/kg in PSAC. In SAC maximum efficacy was obtained with 40 mg/kg praziquantel. Further investigations are required in children with moderate to heavy infections. This trial is registered with International Standard Randomised Controlled Trial Number ISRCTN15280205 .

Neurological Change after Gamma Knife Radiosurgery for Brain Metastases Involving the Motor Cortex

PubMed Central

Park, Chang-Yong; Choi, Hyun-Yong; Lee, Sang-Ryul; Roh, Tae Hoon; Seo, Mi-Ra

2016-01-01

Background Although Gamma Knife radiosurgery (GKRS) can provide beneficial therapeutic effects for patients with brain metastases, lesions involving the eloquent areas carry a higher risk of neurologic deterioration after treatment, compared to those located in the non-eloquent areas. We aimed to investigate neurological change of the patients with brain metastases involving the motor cortex (MC) and the relevant factors related to neurological deterioration after GKRS. Methods We retrospectively reviewed clinical, radiological and dosimetry data of 51 patients who underwent GKRS for 60 brain metastases involving the MC. Prior to GKRS, motor deficits existed in 26 patients (50.9%). The mean target volume was 3.2 cc (range 0.001–14.1) at the time of GKRS, and the mean prescription dose was 18.6 Gy (range 12–24 Gy). Results The actuarial median survival time from GKRS was 19.2±5.0 months. The calculated local tumor control rates at 6 and 12 months after GKRS were 89.7% and 77.4%, respectively. During the median clinical follow-up duration of 12.3±2.6 months (range 1–54 months), 18 patients (35.3%) experienced new or worsened neurologic deficits with a median onset time of 2.5±0.5 months (range 0.3–9.7 months) after GKRS. Among various factors, prescription dose (>20 Gy) was a significant factor for the new or worsened neurologic deficits in univariate (p=0.027) and multivariate (p=0.034) analysis. The managements of 18 patients were steroid medication (n=10), boost radiation therapy (n=5), and surgery (n=3), and neurological improvement was achieved in 9 (50.0%). Conclusion In our series, prescription dose (>20 Gy) was significantly related to neurological deterioration after GKRS for brain metastases involving the MC. Therefore, we suggest that careful dose adjustment would be required for lesions involving the MC to avoid neurological deterioration requiring additional treatment in the patients with limited life expectancy. PMID:27867921

Variability in CT lung-nodule volumetry: Effects of dose reduction and reconstruction methods.

PubMed

Young, Stefano; Kim, Hyun J Grace; Ko, Moe Moe; Ko, War War; Flores, Carlos; McNitt-Gray, Michael F

2015-05-01

Measuring the size of nodules on chest CT is important for lung cancer staging and measuring therapy response. 3D volumetry has been proposed as a more robust alternative to 1D and 2D sizing methods. There have also been substantial advances in methods to reduce radiation dose in CT. The purpose of this work was to investigate the effect of dose reduction and reconstruction methods on variability in 3D lung-nodule volumetry. Reduced-dose CT scans were simulated by applying a noise-addition tool to the raw (sinogram) data from clinically indicated patient scans acquired on a multidetector-row CT scanner (Definition Flash, Siemens Healthcare). Scans were simulated at 25%, 10%, and 3% of the dose of their clinical protocol (CTDIvol of 20.9 mGy), corresponding to CTDIvol values of 5.2, 2.1, and 0.6 mGy. Simulated reduced-dose data were reconstructed with both conventional filtered backprojection (B45 kernel) and iterative reconstruction methods (SAFIRE: I44 strength 3 and I50 strength 3). Three lab technologist readers contoured "measurable" nodules in 33 patients under each of the different acquisition/reconstruction conditions in a blinded study design. Of the 33 measurable nodules, 17 were used to estimate repeatability with their clinical reference protocol, as well as interdose and inter-reconstruction-method reproducibilities. The authors compared the resulting distributions of proportional differences across dose and reconstruction methods by analyzing their means, standard deviations (SDs), and t-test and F-test results. The clinical-dose repeatability experiment yielded a mean proportional difference of 1.1% and SD of 5.5%. The interdose reproducibility experiments gave mean differences ranging from -5.6% to -1.7% and SDs ranging from 6.3% to 9.9%. The inter-reconstruction-method reproducibility experiments gave mean differences of 2.0% (I44 strength 3) and -0.3% (I50 strength 3), and SDs were identical at 7.3%. For the subset of repeatability cases, inter-reconstruction-method mean/SD pairs were (1.4%, 6.3%) and (-0.7%, 7.2%) for I44 strength 3 and I50 strength 3, respectively. Analysis of representative nodules confirmed that reader variability appeared unaffected by dose or reconstruction method. Lung-nodule volumetry was extremely robust to the radiation-dose level, down to the minimum scanner-supported dose settings. In addition, volumetry was robust to the reconstruction methods used in this study, which included both conventional filtered backprojection and iterative methods.

SU-G-TeP4-04: An Automated Monte Carlo Based QA Framework for Pencil Beam Scanning Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, J; Jee, K; Clasie, B

2016-06-15

Purpose: Prior to treating new PBS field, multiple (three) patient-field-specific QA measurements are performed: two 2D dose distributions at shallow depth (M1) and at the tumor depth (M2) with treatment hardware at zero gantry angle; one 2D dose distribution at iso-center (M3) without patient specific devices at the planned gantry angle. This patient-specific QA could be simplified by the use of MC model. The results of MC model commissioning for a spot-scanning system and the fully automated TOPAS/MC-based QA framework will be presented. Methods: We have developed in-house MC interface to access a TPS (Astroid) database from a computer clustermore » remotely. Once a plan is identified, the interface downloads information for the MC simulations, such as patient images, apertures points, and fluence maps and initiates calculations in both the patient and QA geometries. The resulting calculations are further analyzed to evaluate the TPS dose accuracy and the PBS delivery. Results: The Monte Carlo model of our system was validated within 2.0 % accuracy over the whole range of the dose distribution (proximal/shallow part, as well as target dose part) due to the location of the measurements. The averaged range difference after commissioning was 0.25 mm over entire treatment ranges, e.g., 6.5 cm to 31.6 cm. Conclusion: As M1 depths range typically from 1 cm to 4 cm from the phantom surface, The Monte Carlo model of our system was validated within +− 2.0 % in absolute dose level over a whole treatment range. The averaged range difference after commissioning was 0.25 mm over entire treatment ranges, e.g., 6.5 cm to 31.6 cm. This work was supported by NIH/NCI under CA U19 21239.« less

Are Recommended Doses of Acetaminophen Effective for Children Aged 2 to 3 Years? A Pharmacokinetic Modeling Answer.

PubMed

Abourbih, Daniel Asher; Gosselin, Sophie; Villeneuve, Eric; Kazim, Sara

2016-01-01

Acetaminophen (APAP) elixir is a widely used pediatric antipyretic medication. It has been shown that up to 30% of febrile children presenting to a large urban pediatric emergency department received inadequate APAP dosages at home with errors primarily due to age-based dosing. Parental education material in the form of weight-based dosing guides has been proposed; however, validation of current recommended APAP dosages using pharmacokinetic models is needed. This study used a mathematical model of APAP absorption to predict plasma concentrations and to compare them with the range required to reach and achieve antipyresis (10-20 μg/mL). A common APAP preparation (Children's Tylenol Elixir) was tested (children aged 2-3 years, 10.9-15.9 kg). The manufacturer's suggested dose of 160 mg was compared with the standard 10 to 15 mg/kg dose range. The model predicts a peak plasma concentration between 6.38 and 8.55 μg/mL for 10 mg/kg dose and 9.57 and 12.8 μg/mL for 15 mg/kg dose. The manufacturer's suggested dose of 160 mg was tested across the limits of the weight range (10.9-15.9 kg). A peak plasma concentration between 9.36 and 12.6 μg/mL was found for the lower weight limit (10.9 kg child) and 6.42 to 8.61 μg/mL for the upper weight limit (15.9 kg child). With the use of this model, the 10 mg/kg dose does not reach the plasma concentration value for antipyresis (10-20 μg/mL), whereas 15 mg/kg is adequate only if assuming a greater absorption constant. The 160 mg dose is effective only for children weighing 10.9 kg. Individual differences in drug bioavailability, volume of distribution, and absorption/elimination constants undoubtedly exist, and future studies directly measuring plasma APAP concentration and pharmacokinetics are needed. However, these results indicate that dosages for APAP in children should be weight based and manufacturers should review their dosing recommendations.

Validation of a low dose simulation technique for computed tomography images.

PubMed

Muenzel, Daniela; Koehler, Thomas; Brown, Kevin; Zabić, Stanislav; Fingerle, Alexander A; Waldt, Simone; Bendik, Edgar; Zahel, Tina; Schneider, Armin; Dobritz, Martin; Rummeny, Ernst J; Noël, Peter B

2014-01-01

Evaluation of a new software tool for generation of simulated low-dose computed tomography (CT) images from an original higher dose scan. Original CT scan data (100 mAs, 80 mAs, 60 mAs, 40 mAs, 20 mAs, 10 mAs; 100 kV) of a swine were acquired (approved by the regional governmental commission for animal protection). Simulations of CT acquisition with a lower dose (simulated 10-80 mAs) were calculated using a low-dose simulation algorithm. The simulations were compared to the originals of the same dose level with regard to density values and image noise. Four radiologists assessed the realistic visual appearance of the simulated images. Image characteristics of simulated low dose scans were similar to the originals. Mean overall discrepancy of image noise and CT values was -1.2% (range -9% to 3.2%) and -0.2% (range -8.2% to 3.2%), respectively, p>0.05. Confidence intervals of discrepancies ranged between 0.9-10.2 HU (noise) and 1.9-13.4 HU (CT values), without significant differences (p>0.05). Subjective observer evaluation of image appearance showed no visually detectable difference. Simulated low dose images showed excellent agreement with the originals concerning image noise, CT density values, and subjective assessment of the visual appearance of the simulated images. An authentic low-dose simulation opens up opportunity with regard to staff education, protocol optimization and introduction of new techniques.

Fluence-to-Absorbed Dose Conversion Coefficients for Use in Radiological Protection of Embryo and Foetus Against External Exposure to Muons from 20MeV to 50GeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Jing

2008-08-07

This study used the Monte-Carlo code MCNPX to determine mean absorbed doses to the embryo and foetus when the mother is exposed to external muon fields. Monoenergetic muons ranging from 20 MeV to 50 GeV were considered. The irradiation geometries include anteroposterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT), isotropic (ISO), and top-down (TOP). At each of these irradiation geometries, absorbed doses to the foetal body were calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months, respectively. Muon fluence-to-absorbed-dose conversion coefficients were derived for the four prenatal ages. Since such conversion coefficients aremore » yet unknown, the results presented here fill a data gap.« less

Optically stimulated luminescence (OSL) of carbon-doped aluminum oxide (Al{sub 2}O{sub 3}:C) for film dosimetry in radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schembri, V.; Heijmen, B. J. M.

2007-06-15

Introduction and Purpose: Conventional x-ray films and radiochromic films have inherent challenges for high precision radiotherapy dosimetry. Here we have investigated basic characteristics of optically stimulated luminescence (OSL) of irradiated films containing carbon-doped aluminum oxide (Al{sub 2}O{sub 3}:C) for dosimetry in therapeutic photon and electron beams. Materials and Methods: The OSL films consist of a polystyrene sheet, with a top layer of a mixture of single crystals of Al{sub 2}O{sub 3}:C, ground into a powder, and a polyester base. The total thickness of the films is 0.3 mm. Measurements have been performed in a water equivalent phantom, using 4, 6,more » 10, and 18 MV photon beams, and 6-22 MeV electron beams. The studies include assessment of the film response (acquired OSL signal/delivered dose) on delivered dose (linearity), dose rate (1-6 Gy/min), beam quality, field size and depth (6 MV, ranges 4x4-30x30 cm{sup 2}, d{sub max}-35 cm). Doses have been derived from ionization chamber measurements. OSL films have also been compared with conventional x-ray and GafChromic films for dosimetry outside the high dose area, with a high proportion of low dose scattered photons. In total, 787 OSL films have been irradiated. Results: Overall, the OSL response for electron beams was 3.6% lower than for photon beams. Differences between the various electron beam energies were not significant. The 6 and 18 MV photon beams differed in response by 4%. No response dependencies on dose rate were observed. For the 6 MV beam, the field size and depth dependencies of the OSL response were within {+-}2.5%. The observed inter-film response variation for films irradiated with the same dose varied from 1% to 3.2% (1 SD), depending on the measurement day. At a depth of 20 cm, 5 cm outside the 20x20 cm{sup 2} 6 and 18 MV beams, an over response of 17% was observed. In contrast to GafChromic and conventional x-ray films, the response of the Al{sub 2}O{sub 3}:C films is linear in the clinically relevant dose range 0-200 cGy. Conclusions: Measurement of the OSL signal of irradiated films containing Al{sub 2}O{sub 3}:C is a promising technique for film dosimetry in radiotherapy with no or small response variations with dose rate, beam quality, field size and depth, and a linear response from 0 to 200 cGy.« less

Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: Daily and cumulative dose.

PubMed

Palmsten, Kristin; Rolland, Matthieu; Hebert, Mary F; Clowse, Megan E B; Schatz, Michael; Xu, Ronghui; Chambers, Christina D

2018-04-01

To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length. This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated. Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (β: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (β: -2.6 weeks (95%: -3.6, -1.5)). In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose. Copyright © 2018 John Wiley & Sons, Ltd.

Methylphenidate, cognition, and epilepsy: A double-blind, placebo-controlled, single-dose study.

PubMed

Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford

2017-01-31

To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20-62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive "fogginess" (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. NCT02178995. This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints. © 2016 American Academy of Neurology.

SU-E-T-638: Evaluation and Comparison of Landauer Microstar (OSLD) Readers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souri, S; Ahmed, Y; Cao, Y

2014-06-15

Purpose: To evaluate and compare characteristic performance of a new Landauer nanodot Reader with the previous model. Methods: In order to calibrate and test the reader, a set of nanodots were irradiated using a Varian Truebeam Linac. Solid water slabs and bolus were used in the process of irradiation. Calibration sets of nanodots were irradiated for radiation dose ranges: 0 to 10 and 20 to 1000 cGy, using 6MV photons. Additionally, three sets of nanodots were each irradiated using 6MV, 10MV and 15MV beams. For each beam energy, and selected dose in the range of 3 to 1000 cGy, amore » pair of nanodots was irradiated and three readings were obtained with both readers. Results: The analysis shows that for 3 photon beam energies and selected ranges of dose, the calculated absorbed dose agrees well with the expected value. The results illustrate that the new Microstar II reader is a highly consistent system and that the repeated readings provide results with a reasonably small standard deviation. For all practical purposes, the response of system is linear for all radiation beam energies. Conclusion: The Microstar II nanodot reader is consistent, accurate, and reliable. The new hardware design and corresponding software contain several advantages over the previous model. The automatic repeat reading mechanism, that helps improve reproducibility and reduce processing time, and the smaller unit size that renders ease of transport, are two of such features. Present study shows that for high dose ranges a polynomial calibration equation provides more consistent results. A 3rd order polynomial calibration curve was used to analyze the readings of dosimeters exposed to high dose range radiation. It was observed that the results show less error compared to those calculated by using linear calibration curves, as provided by Landauer system software for all dose ranges.« less

Rituximab in refractory myasthenia gravis: extended prospective study results.

PubMed

Beecher, Grayson; Anderson, Dustin; Siddiqi, Zaeem A

2018-05-09

Rituximab appears beneficial in treatment-refractory myasthenia gravis (MG), however, prospective, long-term durability data is lacking. In this prospective, open-label study of rituximab in refractory MG, 22 patients (10 AChR, 9 MuSK, 3 seronegative) received rituximab at baseline, with repeat cycles driven by clinical worsening. Manual muscle testing (MMT) scores and CD19/CD20+ B cell counts were serially monitored. At mean follow-up of 28.8 ± 19.0 months (range=6-66 months), mean MMT scores declined from 10.6 ± 5.4 to 3.3 ± 3.1 (p<0.0001). Mean prednisone dose declined from 25.2 ± 15.1 mg/d to 7.3 ± 7.1 mg/d (p=0.002). Ten relapses occurred, with average time to first relapse of 17.1 ± 5.5 months (range=9-23 months). CD19/CD20+ count recovery did not predict relapse. Three patients experienced prolonged B cell depletion (range=24-45 months) after one cycle. Sustained clinical improvement was associated with rituximab after one cycle, with prolonged time to relapse and reduction in steroid dose. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.

PubMed

Wheeldon, N M; McDevitt, D G; Lipworth, B J

1994-08-01

1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2-adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.

PubMed

Tanaka, Jun; Kasai, Hidefumi; Shimizu, Kenji; Shimasaki, Shigeki; Kumagai, Yuji

2013-03-01

We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range. We used pooled data obtained from two phase I studies and one phase III study performed in Japan. The population pharmacokinetic analysis was performed using NONMEM software. The optimal dose and infusion rate were determined using simulation results obtained using the final model. The therapeutic range for total plasma phenytoin concentration is 10-20 μg/mL. We used a linear two-compartment model with conversion of fosphenytoin to phenytoin. Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight. The dose simulations are as follows. In adult patients, the optimal dose and infusion rate of phenytoin for achieving the therapeutic range was 22.5 mg/kg and 3 mg/kg/min respectively. In pediatric patients, the total plasma concentration of phenytoin was within the therapeutic range for a shorter duration than that in adult patients at 22.5 mg/kg (3 mg/kg/min). However, many pediatric patients showed phenytoin concentration within the toxic range after administration of a dose of 30 mg/kg. The pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium could be described using a linear two-compartment model. The administration of fosphenytoin sodium 22.5 mg/kg at an infusion rate of 3 mg/kg/min was optimal for achieving the desired plasma phenytoin concentration.

Radon activity concentrations and effective doses in ancient Egyptian tombs of the Valley of the Kings.

PubMed

Hafez, A F; Hussein, A S

2001-09-01

Radon concentrations and equilibrium factors were measured in three pharaonic tombs during the year 1998. The tombs, which are open to the public are located in a limestone wadi on the West Bank of the River Nile at Luxor, 650 km south of Cairo. The radon activity concentration and equilibrium factor were measured monthly by two-integral nuclear track detectors (bare and diffusion detectors). Seasonal variation of radon concentrations, with summer maximum and winter minimum were observed in all tombs investigated. The yearly mean radon activity concentrations insidc the tombs ranged from 540 to 3115 Bq m(-3). The mean equilibrium factor over a year was found to be 0.25 and 0.32 inside and at the entrance, respectively. Estimated annual effective doses to tour guides ranged from 0.33 to 1.90 mSv, visitors receive doses from 0.65 to 3.80 microSv per visit. The effective dose to tomb workers did not exceed the 20 mSv yr(-1) limit.

Range and trend of expected toxicity level (ETL) in standard A + B designs: a report from the Children's Oncology Group.

PubMed

Chen, Zhengjia; Krailo, Mark D; Sun, Junfeng; Azen, Stanley P

2009-03-01

The traditional algorithm-based 3+3 designs are most widely used for their practical simplicity in phase I clinical trials. At early stage, a common belief was that the expected toxicity level (ETL) at the maximum tolerated dose (MTD) should be 33% [Storer, B. Design and analysis of phase I clinical trials. Biometrics 1989;45;925-937, Gorden, N., Willson, J. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Statistics in Medicine 1992; 11: 2063-2075, Mick, R. Phase I Clinical Trial Design. In Schilsky, R., Milano, G., Ratain, M., eds. Principles of Antineoplastic Drug Development and Pharmacology New York, NY: Marcel Dekker, 1996; 29-36]. Recently, Kang and Ahn [Kang, S., Ahn, C. The expected toxicity rate at the maximum tolerated dose in the standard phase I cancer clinical trial design. Drug Information Journal 2001; 35:1189-1199, Kang, S., Ahn, C. An investigation of the traditional algorithm-based designs for phase I cancer clinical trials. Drug Information Journal 2002; 36:865-873] found that the ETL is between 17% and 21% and He et al [He, W., Liu, J., Binkowitz, B., Quan, H. A model-based approach in the estimation of the maximum tolerated dose in phase I cancer clinical trials. Statistics in Medicine 2006; 25(12):2027-42] further reported that the ETL ranges from 19% to 24%. However they only investigated designs where the number of dose levels was at most 20. It has practical significance in designing and conducting phase I clinical trial to definitely assess the full range and trend of ETL by all possible number of tested dose levels in traditional algorithm-based A+B designs, especially 3+3 designs. In this simulation study, we originally find that the ETL decreases monotonically from about 30% to 0% as the number of dose levels increase from 3 to infinity, which will correct the inaccuracy in the common belief among phase I trial investigators. To help better design and conduct phase I trials, we create a table as a reference for the association between ETL and number of dose levels considered in a design when the exact shape of the dose-toxicity relationship is not well understood. We conclude that the number of specified dose levels is an important factor affecting substantially the ETL at MTD and recommend that fewer than 20 dose levels be designated.

Vorinostat Combined with High-Dose Gemcitabine, Busulfan, and Melphalan with Autologous Stem Cell Transplantation in Patients with Refractory Lymphomas.

PubMed

Nieto, Yago; Valdez, Benigno C; Thall, Peter F; Ahmed, Sairah; Jones, Roy B; Hosing, Chitra; Popat, Uday; Shpall, Elizabeth J; Qazilbash, Muzaffar; Gulbis, Alison; Anderlini, Paolo; Alousi, Amin; Shah, Nina; Bashir, Qaiser; Liu, Yan; Oki, Yasuhiro; Hagemeister, Frederick; Fanale, Michelle; Dabaja, Bouthaina; Pinnix, Chelsea; Champlin, Richard; Andersson, Borje S

2015-11-01

More active high-dose regimens are needed for refractory/poor-risk relapsed lymphomas. We previously developed a regimen of infusional gemcitabine/busulfan/melphalan, exploiting the synergistic interaction. Its encouraging activity in refractory lymphomas led us to further enhance its use as a platform for epigenetic modulation. We previously observed increased cytotoxicity in refractory lymphoma cell lines when the histone deacetylase inhibitor vorinostat was added to gemcitabine/busulfan/melphalan, which prompted us to clinically study this four-drug combination. Patients ages 12 to 65 with refractory diffuse large B cell lymphoma (DLCL), Hodgkin (HL), or T lymphoma were eligible. Vorinostat was given at 200 mg/day to 1000 mg/day (days -8 to -3). Gemcitabine was infused continuously at 10 mg/m(2)/minute over 4.5 hours (days -8 and -3). Busulfan dosing targeted 4000 μM-minute/day (days -8 to -5). Melphalan was infused at 60 mg/m(2)/day (days -3 and -2). Patients with CD20(+) tumors received rituximab (375 mg/m(2), days +1 and +8). We enrolled 78 patients: 52 DLCL, 20 HL, and 6 T lymphoma; median age 44 years (range, 15 to 65); median 3 prior chemotherapy lines (range, 2 to 7); and 48% of patients had positron emission tomography-positive tumors at high-dose chemotherapy (29% unresponsive). The vorinostat dose was safely escalated up to 1000 mg/day, with no treatment-related deaths. Toxicities included mucositis and dermatitis. Neutrophils and platelets engrafted promptly. At median follow-up of 25 (range, 16 to 41) months, event-free and overall survival were 61.5% and 73%, respectively (DLCL) and 45% and 80%, respectively (HL). In conclusion, vorinostat/gemcitabine/busulfan/melphalan is safe and highly active in refractory/poor-risk relapsed lymphomas, warranting further evaluation. This trial was registered at ClinicalTrials.gov (NCI-2011-02891). Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma.

PubMed

von Tresckow, Bastian; Morschhauser, Franck; Ribrag, Vincent; Topp, Max S; Chien, Caly; Seetharam, Shobha; Aquino, Regina; Kotoulek, Sonja; de Boer, Carla J; Engert, Andreas

2015-04-15

This phase I/II study investigated JNJ-40346527, a selective inhibitor of the colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase as treatment for relapsed or refractory classical Hodgkin lymphoma (cHL). Patients ≥18 years with histopathologically confirmed initial diagnosis of cHL that had relapsed or was refractory after ≥1 appropriate therapies were assigned to sequential cohorts of oral daily doses of JNJ-40346527 (150, 300, 450, 600 mg every day, and 150 mg twice a day). For the dose-escalation phase, the primary endpoint was to establish the recommended phase II dose. Secondary endpoints included safety, pharmacokinetics, and pharmacodynamics. Twenty-one patients [(150 mg: 3; 300 mg: 5; 450 mg: 3, 600 mg: 3) every day, and 150 mg twice a day: 7] were enrolled, 10 men, median age 40 (range, 19-75) years, median number of prior systemic therapies 6 (range, 3-14). No dose-limiting toxicities were observed; maximum-tolerated dose was not established. Best overall response was complete remission in 1 patient (duration, +352 days) and stable disease in 11 patients: (duration, 1.5-8 months). Median number of cycles: 4 (range, 1-16). Most common (≥20% patients) possibly drug-related adverse events (per investigator assessment) were nausea (n = 6), headache, and pyrexia (n = 5 each). JNJ-40346527 exposure increased in near dose-proportional manner over a dose range of 150 to 450 mg every day, but plateaued at 600 mg every day. Target engagement was confirmed (>80% inhibition of CSF-1R phosphorylation, 4 hours after dosing). JNJ-40346527, a selective inhibitor of CSF-1R was well tolerated, and preliminary antitumor results suggested limited activity in monotherapy for the treatment of cHL. ©2015 American Association for Cancer Research.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schnell, E; Ferreira, C; Ahmad, S

Purpose: Accuracy of a RSP-HU calibration curve produced for proton treatment planning is tested by comparing the treatment planning system dose grid to physical doses delivered on film by a Mevion S250 double-scattering proton unit. Methods: A single batch of EBT3 Gafchromic film was used for calibration and measurements. The film calibration curve was obtained using Mevion proton beam reference option 20 (15cm range, 10cm modulation). Paired films were positioned at the center of the spread out Bragg peak (SOBP) in solid water. The calibration doses were verified with an ion chamber, including background and doses from 20cGy to 350cGy.more » Films were scanned in a flatbed Epson-Expression 10000-XL scanner, and analyzed using the red channel. A Rando phantom was scanned with a GE LightSpeed CT Simulator. A single-field proton plan (Eclipse, Varian) was calculated to deliver 171cGy to the pelvis section (heterogeneous region), using a standard 4×4cm aperture without compensator, 7.89cm beam range, and 5.36cm SOBP. Varied depths of the calculated distal 90% isodose-line were recorded and compared. The dose distribution from film irradiated between Rando slices was compared with the calculated plans using RIT v.6.2. Results: Distal 90% isodose-line depth variation between CT scans was 2mm on average, and 4mm at maximum. Fine calculation of this variation was restricted by the dose calculation grid, as well as the slice thickness. Dose differences between calibrated film measurements and calculated doses were on average 5.93cGy (3.5%), with the large majority of differences forming a normal distribution around 3.5cGy (2%). Calculated doses were almost entirely greater than those measured. Conclusion: RSP to HU calibration curve is shown to produce distal depth variation within the margin of tolerance (±4.3mm) across all potential scan energies and protocols. Dose distribution calculation is accurate to 2–4% within the SOBP, including areas of high tissue heterogeneity.« less

SU-E-J-169: The Dosimetric and Temporal Effects of Respiratory-Gated Radiation Therapy in Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rouabhi, O; Gross, B; Xia, J

2015-06-15

Purpose: To evaluate the dosimetric and temporal effects of high dose rate treatment mode for respiratory-gated radiation therapy in lung cancer patients. Methods: Treatment plans from five lung cancer patients (3 nongated (Group 1), 2 gated at 80EX-80IN (Group 2)) were retrospectively evaluated. The maximum tumor motions range from 6–12 mm. Using the same planning criteria, four new treatment plans, corresponding to four gating windows (20EX–20IN, 40EX–40IN, 60EX–60IN, and 80EX–80IN), were generated for each patient. Mean tumor dose (MTD), mean lung dose (MLD), and lung V20 were used to assess the dosimetric effects. A MATLAB algorithm was developed to computemore » treatment time by considering gantry rotation time, time to position collimator leaves, dose delivery time (scaled relative to the gating window), and communication overhead. Treatment delivery time for each plan was estimated using a 500 MU/min dose rate for the original plans and a 1500 MU/min dose rate for the gated plans. Results: Differences in MTD were less than 1Gy across plans for all five patients. MLD and lung V20 were on average reduced between −16.1% to −6.0% and −20.0% to −7.2%, respectively for non-gated plans when compared with the corresponding gated plans, and between − 5.8% to −4.2% and −7.0% to −5.4%, respectively for plans originally gated at 80EX–80IN when compared with the corresponding 20EX-20IN to 60EX– 60IN gated plans. Treatment delivery times of gated plans using high dose rate were reduced on average between −19.7% (−1.9min) to −27.2% (−2.7min) for originally non-gated plans and −15.6% (−0.9min) to −20.3% (−1.2min) for originally 80EX-80IN gated plans. Conclusion: Respiratory-gated radiation therapy in lung cancer patients can reduce lung toxicity, while maintaining tumor dose. Using a gated high-dose-rate treatment, delivery time comparable to non-gated normal-dose-rate treatment can be achieved. This research is supported by Siemens Medical Solutions USA, Inc.« less

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men. Copyright © 2017 by the American Society of Nephrology.

Quantitative evaluation of 3D dosimetry for stereotactic volumetric‐modulated arc delivery using COMPASS

PubMed Central

Manigandan, Durai; Karrthick, Karukkupalayam Palaniappan; Sambasivaselli, Raju; Senniandavar, Vellaingiri; Ramu, Mahendran; Rajesh, Thiyagarajan; Lutz, Muller; Muthukumaran, Manavalan; Karthikeyan, Nithyanantham; Tejinder, Kataria

2014-01-01

The purpose of this study was to evaluate quantitatively the patient‐specific 3D dosimetry tool COMPASS with 2D array MatriXX detector for stereotactic volumetric‐modulated arc delivery. Twenty‐five patients CT images and RT structures from different sites (brain, head & neck, thorax, abdomen, and spine) were taken from CyberKnife Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in CyberKnife. For each patient, linac based volumetric‐modulated arc therapy (VMAT) stereotactic plans were generated in Monaco TPS v3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5–20 Gy per fraction. Target prescription and critical organ constraints were tried to match the delivered treatment plans. Each plan quality was analyzed using conformity index (CI), conformity number (CN), gradient Index (GI), target coverage (TC), and dose to 95% of volume (D95). Monaco Monte Carlo (MC)‐calculated treatment plan delivery accuracy was quantitatively evaluated with COMPASS‐calculated (CCA) dose and COMPASS indirectly measured (CME) dose based on dose‐volume histogram metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using MultiCube phantom. Routine quality assurance of absolute point dose verification was performed to check the overall delivery accuracy. Quantitative analyses of dose delivery verification were compared with pass and fail criteria of 3 mm and 3% distance to agreement and dose differences. Gamma passing rate was compared with 2D fluence verification from MatriXX with MultiCube. Comparison of COMPASS reconstructed dose from measured fluence and COMPASS computed dose has shown a very good agreement with TPS calculated dose. Each plan was evaluated based on dose volume parameters for target volumes such as dose at 95% of volume (D95) and average dose. For critical organs dose at 20% of volume (D20), dose at 50% of volume (D50), and maximum point doses were evaluated. Comparison was carried out using gamma analysis with passing criteria of 3 mm and 3%. Mean deviation of 1.9%±1% was observed for dose at 95% of volume (D95) of target volumes, whereas much less difference was noticed for critical organs. However, significant dose difference was noticed in two cases due to the smaller tumor size. Evaluation of this study revealed that the COMPASS 3D dosimetry is efficient and easy to use for patient‐specific QA of VMAT stereotactic delivery. 3D dosimetric QA with COMPASS provides additional degrees of freedom to check the high‐dose modulated stereotactic delivery with very high precision on patient CT images. PACS numbers: 87.55.Qr, 87.56.Fc PMID:25679152

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Assessment of radiation doses from residential smoke detectors that contain americium-241

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Donnell, F.R.; Etnier, E.L.; Holton, G.A.

1981-10-01

External dose equivalents and internal dose commitments were estimated for individuals and populations from annual distribution, use, and disposal of 10 million ionization chamber smoke detectors that contain 110 kBq (3 ..mu..Ci) americium-241 each. Under exposure scenarios developed for normal distribution, use, and disposal using the best available information, annual external dose equivalents to average individuals were estimated to range from 4 fSv (0.4 prem) to 20 nSv (2 ..mu..rem) for total body and from 7 fSv to 40 nSv for bone. Internal dose commitments to individuals under post disposal scenarios were estimated to range from 0.006 to 80 ..mu..Svmore » (0.0006 to 8 mrem) to total body and from 0.06 to 800 ..mu..Sv to bone. The total collective dose (the sum of external dose equivalents and 50-year internal dose commitments) for all individuals involved with distribution, use, or disposal of 10 million smoke detectors was estimated to be about 0.38 person-Sv (38 person-rem) to total body and 00 ft/sup 2/).« less

SU-F-I-06: Evaluation of Imaging Dose for Modulation Layer Based Dual Energy Cone-Beam CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ju, Eunbin; Ahn, SoHyun; Cho, Samju

Purpose: Dual energy cone beam CT system is finding a variety of promising applications in diagnostic CT, both in imaging of endogenous materials and exogenous materials across a range of body sites. Dual energy cone beam CT system to suggest in this study acquire image by rotating 360 degree with half of the X-ray window covered using copper modulation layer. In the region that covered by modulation layer absorb the low energy X-ray by modulation layer. Relative high energy X-ray passes through the layer and contributes to image reconstruction. Dose evaluation should be carried out in order to utilize suchmore » an imaging acquirement technology for clinical use. Methods: For evaluating imaging dose of modulation layer based dual energy cone beam CT system, Prototype cone beam CT that configured X-ray tube (D054SB, Toshiba, Japan) and detector (PaxScan 2520V, Varian Medical Systems, Palo Alto, CA) is used. A range of 0.5–2.0 mm thickness of modulation layer is implemented in Monte Carlo simulation (MCNPX, ver. 2.6.0, Los Alamos National Laboratory, USA) with half of X-ray window covered. In-house phantom using in this study that has 3 cylindrical phantoms configured water, Teflon air with PMMA covered for verifying the comparability the various material in human body and is implemented in Monte Carlo simulation. The actual dose with 2.0 mm copper covered half of X-ray window is measured using Gafchromic EBT3 film with 5.0 mm bolus for compared with simulative dose. Results: Dose in phantom reduced 33% by copper modulation layer of 2.0 mm. Scattering dose occurred in modulation layer by Compton scattering effect is 0.04% of overall dose. Conclusion: Modulation layer of that based dual energy cone beam CT has not influence on unnecessary scatter dose. This study was supported by the Radiation Safety Research Programs (1305033) through the Nuclear Safety and Security Commission.« less

The relative bioavailability and fasting pharmacokinetics of three formulations of olmesartan medoxomil 20-mg capsules and tablets in healthy Chinese male volunteers: An open-label, randomized-sequence, single-dose, three-way crossover study.

PubMed

Li, Kun-Yan; Liang, Jian-Ping; Hu, Bing-Qiang; Qiu, Yu; Luo, Chen-Hui; Jiang, Yun; Lin, Xiao-Ping; Yang, Nong

2010-08-01

Olmesartan medoxomil is an angiotensin II-receptor antagonist used in the treatment of hypertension. It is a prodrug and is converted to the pharmacologically active compound on de-esterification by arylesterase in the gastrointestinal tract. This study investigated the relative bioavailability and fasting pharmacokinetic properties of olmesartan after single doses of a 20-mg test tablet, a 20-mg test capsule, and a commercially available 20-mg reference tablet in healthy Chinese male volunteers. The study was conducted to satisfy Chinese State Food and Drug Administration regulatory requirements for approval of a generic formulation of olmesartan medoxomil. This study had an open-label, randomized-sequence, single-dose, 3-treatment, 3-period crossover design. Healthy volunteers were randomly assigned in a 1:1:1 ratio to receive a single 20-mg dose of the test tablet, test capsule, or reference tablet, each administered after a 12-hour overnight fast, followed by a 1-week washout period and administration of the alternate formulation. Blood samples were obtained at baseline and at 0.5, 1, 1.5,2,2.5,3,4,6,8,12,24,36, and 48 hours after dosing. Tolerability was assessed based on vital signs and laboratory values obtained before and after administration of study drug. The formulations were assumed to be bioequivalent if the 90% CIs for the log-transformed ratios of C(max), AUC(0-t), and AUC(0-∞) were within the predetermined equivalence range (70%-143% for C(max); 80%-125% for AUC(0-t) and AUC(0-∞)), as established by the Chinese State Food and Drug Administration. Twenty-one healthy male subjects (mean age, 21 years [range, 18-25 years]; weight, 62.1 kg [range, 54.0-80.0 kg]) were enrolled in and completed the study. No period or sequence effect was observed. The mean AUC(0-∞) values for the test tablet, test capsule, and reference tablet were 3993 (1070), 3567 (850), and 3849 (872) ng/mL/h, respectively. The 90% CIs for the log-transformed ratios of test tablet to reference tablet for C(max), AUC(0-48), and AUC(0-∞) were 103.9 to 124.9, 94.0 to 111.5, and 94.4 to 111.7, respectively (all, P = NS). The corresponding 90% CIs for the log-transformed ratios of test capsule to reference tablet were 90.8 to 109.2, 84.9 to 107.9, and 85.1 to 100.7 (all, P = NS). Ten adverse events were reported during the study; 7 subjects complained of pain during blood sampling, and 3 had a blocked venous catheter. No treatment-related adverse events were reported or observed. In this single-dose crossover study in healthy Chinese male volunteers, the test and reference formulations of olmesartan medoxomil 20-mg capsules and tablets met the regulatory criteria for assuming bioequivalence. The 3 formulations were well tolerated. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

[Pharmacokinetic and clinical studies of ceftizoxime in newborn infants].

PubMed

Sato, H; Nakazawa, S; Narita, A; Nakazawa, S; Matsumoto, K; Suzuki, H; Nakanishi, Y; Chikaoka, H; Kamigaki, M; Niino, K

1988-08-01

Pharmacokinetic and clinical studies of ceftizoxime (CZX) were performed in infants given intravenously. The obtained results are summarized as follows. 1. Serum concentrations of CZX in 2 and 3 day-old mature infants given 20 mg/kg by one shot intravenous injection peaked at 49.0 and 57.9 micrograms/ml in 1 hour and decreased to 14.4 and 24.9 micrograms/ml in 8 hours after dosing, respectively. Half-lives were 3.9 and 5.6 hours, respectively. In 5 day-old or older mature infants, peak serum levels ranged from 20.9 to 38.0 micrograms/ml at 1 hour after the injection. Levels of CZX at 8 hours after injection were 1.31 to 7.32 micrograms/ml. Half-lives were 1.6-3.0 hours in all the infants except one. 2. In a 3 day-old premature infant given the same dose by a bolus intravenous injection, the serum level peaked at 45.7 micrograms/ml in 1 hour after the injection. The level at 8 hours after injection was 15.7 micrograms/ml. The half-life was 4.2 hours. In 5-15 day-old premature infants, half-lives were 2.3-3.1 hours in all the infants except one. 3. Serum concentrations of CZX in 1 and 2 day-old infants given 20 mg/kg by intravenous drip infusion peaked at 49.4 to 115.0 micrograms/ml in 1 hour after dosing. Half-lives were rather long, 4.0 and 5.1 hours, in the 2 infants. 4. Peak serum levels and half-lives tended to be lower and shorter in 5 day-old or older ones than in the 3 day-old or younger infants. 5. No changes in the serum concentration were observed even after dosing with 20 mg/kg of continuous one shot intravenous injection. 6. Urinary recovery rates during the first 8 hours (one is 6 hours, two is 9 hours) after 20 mg/kg intravenous bolus injection of CZX tended to be lower in 3 day-old or younger infants than in 5 day-old or older infants. 7. Eleven infants with various bacterial infections were given CZX by intravenous bolus injection or drip infusion. Dosage of CZX used in the present study were 36-148 mg/kg/day in 2-3 divided doses. Duration of treatment ranged from 3 to 12 days. Clinical efficacy of CZX was excellent or good in all the infants with acute bronchitis, acute pneumonia, suspected sepsis infected in uterine, acute otitis media, cellulitis, meningitis caused by Klebsiella pneumoniae and Escherichia coli, acute urinary tract infection and periproctic abscess except 1 case of acute bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)

C-arm flat-panel CT arthrography of the shoulder: Radiation dose considerations and preliminary data on diagnostic performance.

PubMed

Guggenberger, Roman; Ulbrich, Erika J; Dietrich, Tobias J; Scholz, Rosemarie; Kaelin, Pascal; Köhler, Christoph; Elsässer, Thilo; Le Corroller, Thomas; Pfammatter, Thomas; Alkadhi, Hatem; Andreisek, Gustav

2017-02-01

To investigate radiation dose and diagnostic performance of C-arm flat-panel CT (FPCT) versus standard multi-detector CT (MDCT) shoulder arthrography using MRI-arthrography as reference standard. Radiation dose of two different FPCT acquisitions (5 and 20 s) and standard MDCT of the shoulder were assessed using phantoms and thermoluminescence dosimetry. FPCT arthrographies were performed in 34 patients (mean age 44 ± 15 years). Different joint structures were quantitatively and qualitatively assessed by two independent radiologists. Inter-reader agreement and diagnostic performance were calculated. Effective radiation dose was markedly lower in FPCT 5 s (0.6 mSv) compared to MDCT (1.7 mSv) and FPCT 20 s (3.4 mSv). Contrast-to-noise ratios (CNRs) were significantly (p < 0.05) higher in FPCT 20-s versus 5-s protocols. Inter-reader agreements of qualitative ratings ranged between к = 0.47-1.0. Sensitivities for cartilage and rotator cuff pathologies were low for FPCT 5-s (40 % and 20 %) and moderate for FPCT 20-s protocols (75 % and 73 %). FPCT showed high sensitivity (81-86 % and 89-99 %) for bone and acromioclavicular-joint pathologies. Using a 5-s protocol FPCT shoulder arthrography provides lower radiation dose compared to MDCT but poor sensitivity for cartilage and rotator cuff pathologies. FPCT 20-s protocol is moderately sensitive for cartilage and rotator cuff tendon pathology with markedly higher radiation dose compared to MDCT. • FPCT shoulder arthrography is feasible with fluoroscopy and CT in one workflow. • A 5-s FPCT protocol applies a lower radiation dose than MDCT. • A 20-s FPCT protocol is moderately sensitive for cartilage and tendon pathology.

A noise power spectrum study of a new model-based iterative reconstruction system: Veo 3.0.

PubMed

Li, Guang; Liu, Xinming; Dodge, Cristina T; Jensen, Corey T; Rong, X John

2016-09-08

The purpose of this study was to evaluate performance of the third generation of model-based iterative reconstruction (MBIR) system, Veo 3.0, based on noise power spectrum (NPS) analysis with various clinical presets over a wide range of clinically applicable dose levels. A CatPhan 600 surrounded by an oval, fat-equivalent ring to mimic patient size/shape was scanned 10 times at each of six dose levels on a GE HD 750 scanner. NPS analysis was performed on images reconstructed with various Veo 3.0 preset combinations for comparisons of those images reconstructed using Veo 2.0, filtered back projection (FBP) and adaptive statistical iterative reconstruc-tion (ASiR). The new Target Thickness setting resulted in higher noise in thicker axial images. The new Texture Enhancement function achieved a more isotropic noise behavior with less image artifacts. Veo 3.0 provides additional reconstruction options designed to allow the user choice of balance between spatial resolution and image noise, relative to Veo 2.0. Veo 3.0 provides more user selectable options and in general improved isotropic noise behavior in comparison to Veo 2.0. The overall noise reduction performance of both versions of MBIR was improved in comparison to FBP and ASiR, especially at low-dose levels. © 2016 The Authors.

Volumetric modulation arc radiotherapy with flattening filter-free beams compared with static gantry IMRT and 3D conformal radiotherapy for advanced esophageal cancer: a feasibility study.

PubMed

Nicolini, Giorgia; Ghosh-Laskar, Sarbani; Shrivastava, Shyam Kishore; Banerjee, Sushovan; Chaudhary, Suresh; Agarwal, Jai Prakash; Munshi, Anusheel; Clivio, Alessandro; Fogliata, Antonella; Mancosu, Pietro; Vanetti, Eugenio; Cozzi, Luca

2012-10-01

A feasibility study was performed to evaluate RapidArc (RA), and the potential benefit of flattening filter-free beams, on advanced esophageal cancer against intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). The plans for 3D-CRT and IMRT with three to seven and five to seven fixed beams were compared against double-modulated arcs with avoidance sectors to spare the lungs for 10 patients. All plans were optimized for 6-MV photon beams. The RA plans were studied for conventional and flattening filter-free (FFF) beams. The objectives for the planning target volume were the volume receiving ≥ 95% or at most 107% of the prescribed dose of <1% with a dose prescription of 59.4 Gy. For the organs at risk, the lung volume (minus the planning target volume) receiving ≥ 5 Gy was <60%, that receiving 20 Gy was <20%-30%, and the mean lung dose was <15.0 Gy. The heart volume receiving 45 Gy was <20%, volume receiving 30 Gy was <50%. The spinal dose received by 1% was <45 Gy. The technical delivery parameters for RA were assessed to compare the normal and FFF beam characteristics. RA and IMRT provided equivalent coverage and homogeneity, slightly superior to 3D-CRT. The conformity index was 1.2 ± 0.1 for RA and IMRT and 1.5 ± 0.2 for 3D-CRT. The mean lung dose was 12.2 ± 4.5 for IMRT, 11.3 ± 4.6 for RA, and 10.8 ± 4.4 for RA with FFF beams, 18.2 ± 8.5 for 3D-CRT. The percentage of volume receiving ≥ 20 Gy ranged from 23.6% ± 9.1% to 21.1% ± 9.7% for IMRT and RA (FFF beams) and 39.2% ± 17.0% for 3D-CRT. The heart and spine objectives were met by all techniques. The monitor units for IMRT and RA were 457 ± 139, 322 ± 20, and 387 ± 40, respectively. RA with FFF beams showed, compared with RA with normal beams, a ∼20% increase in monitor units per Gray, a 90% increase in the average dose rate, and 20% reduction in beam on time (owing to different gantry speeds). RA demonstrated, compared with conventional IMRT, a similar target coverage and some better dose sparing to the organs at risk; the advantage against conventional 3D-CRT was more evident. RA with FFF beams resulted in minor improvements in plan quality but with the potential for additional useful reduction in the treatment time. Copyright © 2012 Elsevier Inc. All rights reserved.

[Acute toxicity of bemithyl and bromithyl].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

2000-01-01

The experiments on rats showed for bemithyl LD50 = 581.48 (350.17-965.57) mg/kg and for bromithyl LD50 = 1750.30 (1463.07-2093.92) mg/kg (males) and 1584.29 (1280.46-1960.22) mg/kg (females). The therapeutic ratios are 4-6 for both drugs, while the toxicity index is 10-15 for bemithyl and 20 <196> 22 for bromithyl. It was established that ergotropic effects prevail in the toxicity of bemithyl administered in the 20-80 mg/kg dose range, while trophotropic effects are dominating at doses above 100 mg/kg. Bromithyl exhibits a dose-dependent trophotropic effect in the entire dose range.

Response of Nanodot Optically Stimulated Luminescence Dosimeters to Therapeutic Electron Beams.

PubMed

Ponmalar, Y Retna; Manickam, Ravikumar; Sathiyan, S; Ganesh, K M; Arun, R; Godson, Henry Finlay

2017-01-01

Response of Al 2 O 3 :C-based nanoDot optically stimulated luminescence (OSL) dosimeter was studied for the dosimetry of 6, 9, 12, 16, and 20 MeV therapeutic electron beams. With reference to ionization chamber, no change in the response was observed with the change in the energy of electron beams for the field size from 6 cm × 6 cm to 25 cm × 25 cm, dose rates from 100 MU/min to 600 MU/min, and the linearity in the response up to 300 cGy. The fading of the transient signal was higher for 20 MeV electron beam than that of 6 MeV electron beam by about 5% as compared to value at 20 min after irradiation. The depletion of OSL signal per readout in 200 successive readouts was also found to change with dose and energy of electron beam from 6 MeV (9% and 12% per readout at 2 and 10 Gy, respectively) to 20 MeV (9% and 16% at 2 and 10 Gy, respectively). The OSL sensitivity changed in the range from 2% to 6% with accumulated doses from 2 to 8 Gy and with electron energy from 6 to 20 MeV, but the sensitivity could be reset using an optical annealing treatment. Although negligible fading for postirradiation storage from 20 min to several months, acceptable precision and linearity in the desired range, and high reproducibility makes nanoDot dosimeters very attractive for the dosimetry of therapeutic electron beams, a note should be made for changes in sensitivity at doses beyond 2 Gy and electron beams energy dependence in reuse, short-term fading, and signal depletion on repeated readout.

Response of Nanodot Optically Stimulated Luminescence Dosimeters to Therapeutic Electron Beams

PubMed Central

Ponmalar, Y. Retna; Manickam, Ravikumar; Sathiyan, S.; Ganesh, K. M.; Arun, R.; Godson, Henry Finlay

2017-01-01

Response of Al2O3:C-based nanoDot optically stimulated luminescence (OSL) dosimeter was studied for the dosimetry of 6, 9, 12, 16, and 20 MeV therapeutic electron beams. With reference to ionization chamber, no change in the response was observed with the change in the energy of electron beams for the field size from 6 cm × 6 cm to 25 cm × 25 cm, dose rates from 100 MU/min to 600 MU/min, and the linearity in the response up to 300 cGy. The fading of the transient signal was higher for 20 MeV electron beam than that of 6 MeV electron beam by about 5% as compared to value at 20 min after irradiation. The depletion of OSL signal per readout in 200 successive readouts was also found to change with dose and energy of electron beam from 6 MeV (9% and 12% per readout at 2 and 10 Gy, respectively) to 20 MeV (9% and 16% at 2 and 10 Gy, respectively). The OSL sensitivity changed in the range from 2% to 6% with accumulated doses from 2 to 8 Gy and with electron energy from 6 to 20 MeV, but the sensitivity could be reset using an optical annealing treatment. Although negligible fading for postirradiation storage from 20 min to several months, acceptable precision and linearity in the desired range, and high reproducibility makes nanoDot dosimeters very attractive for the dosimetry of therapeutic electron beams, a note should be made for changes in sensitivity at doses beyond 2 Gy and electron beams energy dependence in reuse, short-term fading, and signal depletion on repeated readout. PMID:28405107

SU-F-T-185: Study of the Robustness of a Proton Arc Technique Based On PBS Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Z; Zheng, Y

Purpose: One potential technique to realize proton arc is through using PBS beams from many directions to form overlaid Bragg peak (OBP) spots and placing these OBP spots throughout the target volume to achieve desired dose distribution. In this study, we analyzed the robustness of this proton arc technique. Methods: We used a cylindrical water phantom of 20 cm in radius in our robustness analysis. To study the range uncertainty effect, we changed the density of the phantom by ±3%. To study the setup uncertainty effect, we shifted the phantom by 3 & 5 mm. We also combined the rangemore » and setup uncertainties (3mm/±3%). For each test plan, we performed dose calculation for the nominal and 6 disturbed scenarios. Two test plans were used, one with single OBP spot and the other consisting of 121 OBP spots covering a 10×10cm{sup 2} area. We compared the dose profiles between the nominal and disturbed scenarios to estimate the impact of the uncertainties. Dose calculation was performed with Gate/GEANT based Monte Carlo software in cloud computing environment. Results: For each of the 7 scenarios, we simulated 100k & 10M events for plans consisting of single OBP spot and 121 OBP spots respectively. For single OBP spot, the setup uncertainty had minimum impact on the spot’s dose profile while range uncertainty had significant impact on the dose profile. For plan consisting of 121 OBP spots, similar effect was observed but the extent of disturbance was much less compared to single OBP spot. Conclusion: For PBS arc technique, range uncertainty has significantly more impact than setup uncertainty. Although single OBP spot can be severely disturbed by the range uncertainty, the overall effect is much less when a large number of OBP spots are used. Robustness optimization for PBS arc technique should consider range uncertainty with priority.« less

Single-Fraction Intraoperative Radiotherapy for Breast Cancer: Early Cosmetic Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beal, Kathryn; McCormick, Beryl; Zelefsky, Michael J.

2007-09-01

Purpose: To evaluate the cosmetic outcome of patients treated with wide local excision and intraoperative radiotherapy for early-stage breast cancer. Methods and Materials: A total of 50 women were treated on a pilot study to evaluate the feasibility of intraoperative radiotherapy at wide local excision. The eligibility criteria included age >60, tumor size {<=}2.0 cm, clinically negative lymph nodes, and biopsy-established diagnosis. After wide local excision, a custom breast applicator was placed in the excision cavity, and a dose of 20 Gy was prescribed to a depth of 1 cm. After 18 patients were treated, the dose was constrained laterallymore » to 18 Gy. The cosmetic outcome was evaluated by photographs at baseline and at 6 and 12 months postoperatively. Four examiners graded the photographs for symmetry, edema, discoloration, contour, and scarring. The grades were evaluated in relationship to the volume of irradiated tissue, tumor location, and dose at the lateral aspects of the cavity. Results: The median volume of tissue receiving 100% of the prescription dose was 47 cm{sup 3} (range, 20-97 cm{sup 3}). Patients with {<=}47 cm{sup 3} of treated tissue had better cosmetic outcomes than did the women who had >47 cm{sup 3} of treated tissue. Women who had received 18 Gy at the lateral aspects of their cavities had better cosmetic outcomes than did women who had received 20 Gy at the lateral aspects. When comparing the 6- and 12-month results, the scores remained stable for 63%, improved for 17%, and worsened for 20%. Conclusion: Intraoperative radiotherapy appears feasible for selected patients. A favorable cosmetic outcome appears to be related to a smaller treatment volume. The cosmetic outcome is acceptable, although additional follow-up is necessary.« less

Validation of a Low Dose Simulation Technique for Computed Tomography Images

PubMed Central

Muenzel, Daniela; Koehler, Thomas; Brown, Kevin; Žabić, Stanislav; Fingerle, Alexander A.; Waldt, Simone; Bendik, Edgar; Zahel, Tina; Schneider, Armin; Dobritz, Martin; Rummeny, Ernst J.; Noël, Peter B.

2014-01-01

Purpose Evaluation of a new software tool for generation of simulated low-dose computed tomography (CT) images from an original higher dose scan. Materials and Methods Original CT scan data (100 mAs, 80 mAs, 60 mAs, 40 mAs, 20 mAs, 10 mAs; 100 kV) of a swine were acquired (approved by the regional governmental commission for animal protection). Simulations of CT acquisition with a lower dose (simulated 10–80 mAs) were calculated using a low-dose simulation algorithm. The simulations were compared to the originals of the same dose level with regard to density values and image noise. Four radiologists assessed the realistic visual appearance of the simulated images. Results Image characteristics of simulated low dose scans were similar to the originals. Mean overall discrepancy of image noise and CT values was −1.2% (range −9% to 3.2%) and −0.2% (range −8.2% to 3.2%), respectively, p>0.05. Confidence intervals of discrepancies ranged between 0.9–10.2 HU (noise) and 1.9–13.4 HU (CT values), without significant differences (p>0.05). Subjective observer evaluation of image appearance showed no visually detectable difference. Conclusion Simulated low dose images showed excellent agreement with the originals concerning image noise, CT density values, and subjective assessment of the visual appearance of the simulated images. An authentic low-dose simulation opens up opportunity with regard to staff education, protocol optimization and introduction of new techniques. PMID:25247422

Methylphenidate, cognition, and epilepsy

PubMed Central

Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J.; Loring, David W.; Meador, Kimford

2017-01-01

Objective: To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. Methods: This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Results: Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20–62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive “fogginess” (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. Conclusions: This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. ClinicalTrials.gov identifier: NCT02178995. Classification of evidence: This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints. PMID:28031390

Comparison of Nine Statistical Model Based Warfarin Pharmacogenetic Dosing Algorithms Using the Racially Diverse International Warfarin Pharmacogenetic Consortium Cohort Database

PubMed Central

Liu, Rong; Li, Xi; Zhang, Wei; Zhou, Hong-Hao

2015-01-01

Objective Multiple linear regression (MLR) and machine learning techniques in pharmacogenetic algorithm-based warfarin dosing have been reported. However, performances of these algorithms in racially diverse group have never been objectively evaluated and compared. In this literature-based study, we compared the performances of eight machine learning techniques with those of MLR in a large, racially-diverse cohort. Methods MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied in warfarin dose algorithms in a cohort from the International Warfarin Pharmacogenetics Consortium database. Covariates obtained by stepwise regression from 80% of randomly selected patients were used to develop algorithms. To compare the performances of these algorithms, the mean percentage of patients whose predicted dose fell within 20% of the actual dose (mean percentage within 20%) and the mean absolute error (MAE) were calculated in the remaining 20% of patients. The performances of these techniques in different races, as well as the dose ranges of therapeutic warfarin were compared. Robust results were obtained after 100 rounds of resampling. Results BART, MARS and SVR were statistically indistinguishable and significantly out performed all the other approaches in the whole cohort (MAE: 8.84–8.96 mg/week, mean percentage within 20%: 45.88%–46.35%). In the White population, MARS and BART showed higher mean percentage within 20% and lower mean MAE than those of MLR (all p values < 0.05). In the Asian population, SVR, BART, MARS and LAR performed the same as MLR. MLR and LAR optimally performed among the Black population. When patients were grouped in terms of warfarin dose range, all machine learning techniques except ANN and LAR showed significantly higher mean percentage within 20%, and lower MAE (all p values < 0.05) than MLR in the low- and high- dose ranges. Conclusion Overall, machine learning-based techniques, BART, MARS and SVR performed superior than MLR in warfarin pharmacogenetic dosing. Differences of algorithms’ performances exist among the races. Moreover, machine learning-based algorithms tended to perform better in the low- and high- dose ranges than MLR. PMID:26305568

Individual variation in botulism.

PubMed Central

Smith, G. R.

1986-01-01

Mice were treated per os with one oral LD100 of toxic filtrate from a culture of Clostridium botulinum type C. The period between dosing and the first appearance of clinical signs varied greatly (2-31 h) from one animal to another. The duration of the pre-clinical and clinical phases together ranged from 5.5 to greater than 55 h. The duration of the clinical phase alone ranged from 1.25 to greater than 24 h, except for a minority of mice in which death occurred suddenly from apparent heart failure with no premonitory signs 4.75-31 h after dosing. Toxaemia was demonstrable in all mice that had just begun to show a clinical response 3.75-6.5 h after dosing, and in some that had not. Outside these time limits toxaemia was demonstrable only rarely, and beyond 12 h after dosing never. Therefore the many (approximately 50%) mice that began to show clinical signs more than 12 h after dosing had no demonstrable toxaemia throughout the entire clinical phase of the disease. The concentrations of toxin demonstrated in the blood ranged from less than 5 to greater than or equal to 20 (but less than 40) intravenous mouse-lethal doses/ml. PMID:3741778

TU-FG-BRB-05: A 3 Dimensional Prompt Gamma Imaging System for Range Verification in Proton Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Draeger, E; Chen, H; Polf, J

2016-06-15

Purpose: To report on the initial developments of a clinical 3-dimensional (3D) prompt gamma (PG) imaging system for proton radiotherapy range verification. Methods: The new imaging system under development consists of a prototype Compton camera to measure PG emission during proton beam irradiation and software to reconstruct, display, and analyze 3D images of the PG emission. For initial test of the system, PGs were measured with a prototype CC during a 200 cGy dose delivery with clinical proton pencil beams (ranging from 100 MeV – 200 MeV) to a water phantom. Measurements were also carried out with the CC placedmore » 15 cm from the phantom for a full range 150 MeV pencil beam and with its range shifted by 2 mm. Reconstructed images of the PG emission were displayed by the clinical PG imaging software and compared to the dose distributions of the proton beams calculated by a commercial treatment planning system. Results: Measurements made with the new PG imaging system showed that a 3D image could be reconstructed from PGs measured during the delivery of 200 cGy of dose, and that shifts in the Bragg peak range of as little as 2 mm could be detected. Conclusion: Initial tests of a new PG imaging system show its potential to provide 3D imaging and range verification for proton radiotherapy. Based on these results, we have begun work to improve the system with the goal that images can be produced from delivery of as little as 20 cGy so that the system could be used for in-vivo proton beam range verification on a daily basis.« less

[Neutron Dosimetry System Using CR-39 for High-energy X-ray Radiation Therapy].

PubMed

Yabuta, Kazutoshi; Monzen, Hajime; Tamura, Masaya; Tsuruta, Takao; Itou, Tetsuo; Nohtomi, Akihiro; Nishimura, Yasumasa

2014-01-01

Neutrons are produced during radiation treatment by megavolt X-ray energies. However, it is difficult to measure neutron dose especially just during the irradiation. Therefore, we have developed a system for measuring neutrons with the solid state track detector CR-39, which is free from the influence of the X-ray beams. The energy spectrum of the neutrons was estimated by a Monte Carlo simulation method, and the estimated neutron dose was corrected by the contribution ratio of each energy. Pit formation rates of CR-39 ranged from 2.3 x 10(-3) to 8.2 x 10(-3) for each detector studied. According to the estimated neutron energy spectrum, the energy values for calibration were 144 keV and 515keV, and the contribution ratios were approximately 40:60 for 10 MV photons and 20:70 for photons over 15 MV. Neutron doses measured in the center of a high-energy X-ray field were 0.045 mSv/Gy for a 10 MV linear accelerator and 0.85 mSv/Gy for a 20 MV linear accelerator. We successfully developed the new neutron dose measurement system using the solid track detector, CR-39. This on-time neutron measurement system allows users to measure neutron doses produced in the radiation treatment room more easily.

MO-F-CAMPUS-T-02: Dosimetric Accuracy of the CrystalBallâ„¢: New Reusable Radiochromic Polymer Gel Dosimeter for Patient QA in Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avery, S; Kraus, J; Lin, L

2015-06-15

Purpose: To evaluate the accuracy of monoexponential normalization in a new class of commercial, reusable, human-soft-tissue-equivalent, radiochromic polymer gel dosimeters for patient-specific QA in proton therapy. Methods: Eight formulations of the dosimeter (sealed in glass spheres of 166 mm OD), were exposed to a 150 MeV proton beam (5 cm x 5 cm square field, range 15 cm, modulation10 cm), with max dose ranging from 2.5 Gy to 20 Gy, depending on formulation. Exposed dosimeters were promptly placed in the commercial OCTOPUS™ laser CT scanner which was programmed to scan the central slice every 5 minutes for 20 hours (15more » seconds per slice scan). This procedure was repeated several times. Reconstructed data were analyzed using the log-lin scale to determine the time range over which a monoexponential relaxation model could be applied. Next, a simple test plan was devised and delivered to each dosimeter. The OCTOPUS™ was programmed to rescan the central slice at the end of each volume scan, for signal relaxation reference. Monoexponential normalization was applied to sinograms before FBP reconstruction. Dose calibration was based on a volume-lookup table built within the central spherical volume of 12 cm diameter. 3D gamma and sigma passing rates were measured at 3%/3mm criteria down to 50% isodose. Results: Approximately monoexponential signal relaxation time ranges from 25 minutes to 3.5 hours, depending on formulation, followed by a slower-relaxation component. Noise in reconstructed OD/cm images is less than 0.5%. Dose calibration accuracy is better than 99%. Measured proton PDDs demonstrate absence of Bragg-peak quenching. Estimated number of useful cycles is at least 20, with a theoretical limit above 100. 3D gamma and sigma passing rates exceed 95%. Conclusion: Monoexponential normalization was found to yield adequate dosimetric accuracy in the new class of commercial radiochromic polymer gel dosimeters for patient QA in proton therapy.« less

Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors

PubMed Central

Jimeno, Antonio; Weiss, Glen J.; Miller, Wilson H.; Gettinger, Scott; Eigl, Bernard J.C.; Chang, Anne Lynne S.; Dunbar, Joi; Devens, Shannon; Faia, Kerrie; Skliris, Georgios; Kutok, Jeff; Lewis, Karl D.; Tibes, Raoul; Sharfman, William H.; Ross, Robert W.; Rudin, Charles M.

2013-01-01

Purpose To conduct a first-in-human phase I study to determine the dose-limiting toxicities (DLT), characterize the pharmacokinetic profile, and document the antitumor activity of IPI-926, a new chemical entity that inhibits the Hedgehog pathway (HhP). Experimental Design Patients with solid tumors refractory to standard therapy were given IPI-926 once daily (QD) by mouth in 28-day cycles. The starting dose was 20 mg, and an accelerated titration schedule was used until standard 3 + 3 dose-escalation cohorts were implemented. Pharmacokinetics were evaluated on day −7 and day 22 of cycle 1. Results Ninety-four patients (32F, 62M; ages, 39–87) received doses ranging from 20 to 210 mg QD. Dose levels up to and including 160 mg administered QD were well tolerated. Toxicities consisted of reversible elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin, fatigue, nausea, alopecia, and muscle spasms. IPI-926 was not associated with hematologic toxicity. IPI-926 pharmacokinetics were characterized by a slow absorption (Tmax = 2–8 hours) and a terminal half-life (t1/2) between 20 and 40 hours, supporting QD dosing. Of those HhP inhibitor-naïve patients with basal cell carcinoma (BCC) who received more than one dose of IPI-926 and had a follow-up clinical or Response Evaluation Criteria in Solid Tumors (RECIST) assessment, nearly a third (8 of 28 patients) showed a response to IPI-926 at doses ≥130 mg. Conclusions IPI-926 was well tolerated up to 160 mg QD within 28-day cycles, which was established as the recommended phase II dose and schedule for this agent. Single-agent activity of IPI-926 was observed in HhP inhibitor–naïve patients with BCC. PMID:23575478

Quality assurance of proton beams using a multilayer ionization chamber system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhanesar, Sandeep; Sahoo, Narayan; Kerr, Matthew

2013-09-15

Purpose: The measurement of percentage depth-dose (PDD) distributions for the quality assurance of clinical proton beams is most commonly performed with a computerized water tank dosimetry system with ionization chamber, commonly referred to as water tank. Although the accuracy and reproducibility of this method is well established, it can be time-consuming if a large number of measurements are required. In this work the authors evaluate the linearity, reproducibility, sensitivity to field size, accuracy, and time-savings of another system: the Zebra, a multilayer ionization chamber system.Methods: The Zebra, consisting of 180 parallel-plate ionization chambers with 2 mm resolution, was used tomore » measure depth-dose distributions. The measurements were performed for scattered and scanned proton pencil beams of multiple energies delivered by the Hitachi PROBEAT synchrotron-based delivery system. For scattered beams, the Zebra-measured depth-dose distributions were compared with those measured with the water tank. The principal descriptors extracted for comparisons were: range, the depth of the distal 90% dose; spread-out Bragg peak (SOBP) length, the region between the proximal 95% and distal 90% dose; and distal-dose fall off (DDF), the region between the distal 80% and 20% dose. For scanned beams, the Zebra-measured ranges were compared with those acquired using a Bragg peak chamber during commissioning.Results: The Zebra demonstrated better than 1% reproducibility and monitor unit linearity. The response of the Zebra was found to be sensitive to radiation field sizes greater than 12.5 × 12.5 cm; hence, the measurements used to determine accuracy were performed using a field size of 10 × 10 cm. For the scattered proton beams, PDD distributions showed 1.5% agreement within the SOBP, and 3.8% outside. Range values agreed within −0.1 ± 0.4 mm, with a maximum deviation of 1.2 mm. SOBP length values agreed within 0 ± 2 mm, with a maximum deviation of 6 mm. DDF values agreed within 0.3 ± 0.1 mm, with a maximum deviation of 0.6 mm. For the scanned proton pencil beams, Zebra and Bragg peak chamber range values demonstrated agreement of 0.0 ± 0.3 mm with a maximum deviation of 1.3 mm. The setup and measurement time for all Zebra measurements was 3 and 20 times less, respectively, compared to the water tank measurements.Conclusions: Our investigation shows that the Zebra can be useful not only for fast but also for accurate measurements of the depth-dose distributions of both scattered and scanned proton beams. The analysis of a large set of measurements shows that the commonly assessed beam quality parameters obtained with the Zebra are within the acceptable variations specified by the manufacturer for our delivery system.« less

Natural radioactivity in soil in the Baluchistan province of Pakistan.

PubMed

Mujahid, S A; Hussain, S

2010-08-01

The measurements of natural radioactivity and the assessment of radiological hazards in the soil samples of Baluchistan province of Pakistan have been carried out using HPGe detector. The soil gas radon activities in these areas have also been measured using lucas cell technique. The measured activities of (226)Ra, (232)Th and (40)K were found in the range of 15-27, 20-37 and 328-648 Bq kg(-1), respectively. The calculated absorbed dose rate in air and the annual effective dose were in the range of 35-59 nGy h(-1) and 0.17-0.29 mSv, respectively. Radon activity in the soil gas was found in the range of 357-2476 Bq m(-3).

131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin’s lymphoma: radiation dose to the testes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hattori, Naoya; Gopal, Ajay K.; Shields, Andrew T.

Purpose: To investigate radiation doses to the testes delivered by a radiolabeled anti-CD20 antibody and its effects on male sex hormone levels. Materials and methods: Testicular uptake and retention of 131I-tositumomab were measured, and testicular absorbed doses were calculated for 67 male patients (54+/-11 years of age) with non-Hodgkin's lymphoma who had undergone myeloablative radioimmunotherapy (RIT) using 131I-tositumomab. Time-activity curves for the major organs, testes, and whole body were generated from planar imaging studies. In a subset of patients, male sex hormones were measured before and 1 year after the therapy. Results: The absorbed dose to the testes showed considerablemore » variability (range=4.4-70.2 Gy). Pretherapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction [4.6+/-1.8 nmol/l (pre-RIT) vs. 3.8+/-2.9 nmol/l (post-RIT), P<0.05]. Patients receiving higher radiation doses to the testes (>=25 Gy) showed a greater reduction [4.7+/-1.6 nmol/l (pre-RIT) vs. 3.3+/-2.7 nmol/l (post-RIT), P<0.05] compared with patients receiving lower doses (<25 Gy), who showed no significant change in total testosterone levels. Conclusion: The testicular radiation absorbed dose varied highly among individual patients. Finally, patients receiving higher doses to the testes were more likely to show post-RIT suppression of testosterone levels.« less

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, Damodar, E-mail: damodar.pokhrel@uky.edu; Sood, Sumit; McClinton, Christopher

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planningmore » target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R{sub 50%} values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9 Gy, range: 5.9 to 10.9 Gy); dose to 0.35 cc of spinal cord (average: 7.62 ± 1.7 Gy, range: 5.4 to 9.6 Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5 Gy, range: 3.5 to 8.5 Gy) less than 14, 10, and 10 Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3 Gy, range: 1.5 to 14.9 Gy) and dose to 5 cc of esophagus (average: 7.43 ± 3.8 Gy, range: 1.1 to 11.8 Gy) were kept less than protocol requirements 16 Gy and 11.9 Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5 Gy, range: 1.3 to 10.2 Gy) and dose to 15 cc of heart (average: 2.23 ± 1.8 Gy, range: 0.3 to 5.6 Gy) less than 22 and 16 Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2 mm criteria and 98.3 ± 0.8%, on average, with 3%/3 mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.« less

Long-term follow-up studies of Gamma Knife surgery for patients with neurofibromatosis Type 2.

PubMed

Sun, Shibin; Liu, Ali

2014-12-01

The aim of this study was to evaluate long-term clinical outcomes after Gamma Knife surgery (GKS) for patients with neurofibromatosis Type 2 (NF2) and the role of GKS in the management of NF2. From December 1994 through December 2008, a total of 46 patients (21 male, 25 female) with NF2 underwent GKS and follow-up evaluation for at least 5 years at the Gamma Knife Center of the Beijing Neurosurgical Institute. GKS was performed using the Leksell Gamma Knife Models B and C. The mean age of the patients was 30 years (range 13-59 years). A family history of NF2 was found for 9 (20%) patients. The NF2 phenotype was thought to be Wishart for 20 (44%) and Feiling-Gardner for 26 (56%) patients. Among these 46 patients, GKS was performed to treat 195 tumors (73 vestibular schwannomas and 122 other tumors including other schwannomas and meningiomas). For vestibular schwannomas, the mean volume was 5.1 cm(3) (median 3.6 cm(3), range 0.3-27.3 cm(3)), the mean margin dose was 12.9 Gy (range 10-14 Gy), and the mean maximum dose was 27.3 Gy (range 16.2-40 Gy). For other tumors, the mean volume was 1.7 cm(3) (range 0.3-5.5 cm(3)), the mean margin dose was 13.3 Gy (range 11-14 Gy), and the mean maximum dose was 26.0 Gy (range 18.0-30.4 Gy). The median duration of follow-up was 109 months (range 8-195 months). For the 73 vestibular schwannomas that underwent GKS, the latest follow-up MR images demonstrated regression of 30 (41%) tumors, stable size for 31 (43%) tumors, and enlargement of 12 (16%) tumors. The total rate of tumor control for bilateral vestibular schwannomas in patients with NF2 was 84%. Of the 122 other types of tumors that underwent GKS, 103 (85%) showed no tumor enlargement. The rate of serviceable hearing preservation after GKS was 31.9% (15/47). The actuarial rates for hearing preservation at 3 years, 5 years, 10 years, and 15 years were 98%, 93%, 44%, and 17%, respectively. Of the 46 patients, 22 (48%) became completely bilaterally deaf, 17 (37%) retained unilateral serviceable hearing, and 7 (15%) retained bilateral serviceable hearing. The mean history of the disease course was 12 years (range 5-38 years). GKS was confirmed to provide long-term local tumor control for small- to medium-sized vestibular schwannomas and other types of tumors, although vestibular schwannomas in patients with NF2 responded less well than did unilateral sporadic vestibular schwannomas. Phenotype is the most strongly predictive factor of final outcome after GKS for patients with NF2. The risk for loss of hearing is high, whereas the risk for other cranial nerve complications is low.

Risperidone Dosing in Children and Adolescents with Autistic Disorder: A Double-Blind, Placebo-Controlled Study

ERIC Educational Resources Information Center

Kent, Justine M.; Kushner, Stuart; Ning, Xiaoping; Karcher, Keith; Ness, Seth; Aman, Michael; Singh, Jaskaran; Hough, David

2013-01-01

Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5-17 years), received risperidone (low-dose: 0.125 mg/day [20 to <45 kg], 0.175 mg/day [>45 kg] or high-dose: 1.25 mg/day [20 to <45 kg], 1.75 mg/day [>45 kg]) or placebo. Mean baseline (range 27-29) to endpoint change…

Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, B.; Huang, R.; Kuang, A.

2011-10-15

Purpose: The present study was conducted to investigate salivary iodine kinetics and dosimetry during repeated courses of radioiodine ({sup 131}I) therapy for differentiated thyroid cancer (DTC). Such data could provide a better understanding of the mechanisms of {sup 131}I induced salivary toxicity and help to develop appropriate methods to reduce this injury. Methods: Seventy-eight consecutive DTC patients (mean age 45 {+-} 17 years, 60%, female) undergoing {sup 131}I therapy for remnant ablation or metastatic tumors were prospectively recruited. Planar quantitative scintigraphy of head-neck images was serially acquired after administration of 2.9-7.4 GBq of {sup 131}I to assess kinetics in themore » salivary glands of patients. Salivary absorbed doses were calculated based on the schema of Medical Internal Radiation Dosimetry. Results: The maximum uptakes in percentage of administered {sup 131}I activity per kilogram of gland tissue (%/kg) were 12.9% {+-} 6.5%/kg (range, 0.4%-37.3%/kg) and 12.3% {+-} 6.2%/kg (range, 0.4%-35.1%/kg) for the parotid and submandibular glands, respectively. Statistically significant correlations of maximum uptake versus cumulative activity (r = -0.74, P < 0.01, for the parotid glands; r = -0.71, P < 0.01, for the submandibular glands) and treatment cycle (P < 0.001, for both gland types) were found. The effective half-lives of {sup 131}I in the parotid and submandibular glands were 9.3 {+-} 3.5 h (range, 1.5-19.8 h) and 8.6 {+-} 3.2 h (range, 0.8-18.0 h), respectively. A statistically significant correlation was observed between effective half-life with cumulative activity (r = 0.37, P < 0.01) and treatment cycle (P = 0.03) only for the parotid glands. The calculated absorbed doses were 0.20 {+-} 0.10 mGy/MBq (range, 0.01-0.92 mGy/MBq) and 0.25 {+-} 0.09 mGy/MBq (range, 0.01-1.52 mGy/MBq) for the parotid and submandibular glands, respectively. The photon contribution to the salivary absorbed dose was minimal in relation to the beta dose contribution. Photon-absorbed dose fractions of total absorbed dose were 4.9% {+-} 1.3% (range, 1.1%-8.7%) and 3.7% {+-} 2.5% (range, 0.8%-7.9%) for the parotid and submandibular glands, respectively. Conclusions: The iodine uptake of salivary glands is continuously reduced during the courses of therapy. The phenomenon of hyper-radiosensitivity may to some extent account for the occurrence of salivary gland hypofunction at very low radiation doses with low dose rates in {sup 131}I therapy. On the other hand, failure to incorporate a nonuniform and preferential uptake by salivary gland ductal cells may result in underestimating the actual dose for the critical tissue. Other methods, including {sup 124}I voxel-based dosimetry, are warranted to further investigate the {sup 131}I-induced salivary gland toxicity.« less

Role of radiosurgery in craniopharyngiomas: a preliminary report.

PubMed

Amendola, Beatriz E; Wolf, Aizik; Coy, Sammie R; Amendola, Marco A

2003-08-01

The purpose of this retrospective review is to evaluate our experience using radiosurgery in the management of craniopharyngiomas. Fourteen patients, 6 males and 8 females, ages ranging from 3 to 44 years of age, were treated with radiosurgery from February 1994 through December 2000 for primary or recurrent craniopharyngioma. There were two adults and 12 children. All patients were treated with the Leksell Gamma units Model U or C. The mean minimum dose was 14 Gy ranging from 11 to 20 Gy and the mean maximum dose was 29 Gy ranging from 24 to 40 Gy. Volume of treatment ranged from 0.1 to 26.5 cm(3). The dose to critical structures was below 8 Gy to the optic chiasm and below 14 Gy to the brain stem. One of the 14 patients had previous conventional radiation therapy. All patients are alive and with out evidence of recurrent disease 6-86 months after treatment. Only two patients required retreatment. Although craniopharyngioma is a benign tumor, its location makes even advanced microsurgical techniques difficult to perform. Radiosurgery obviates the shortcomings of surgical resection near the hypothalamic-pituitary axis without the morbidity of open surgery. Copyright 2003 Wiley-Liss, Inc.

A Phase I Study of Hepatic Arterial Infusion of Nab-Paclitaxel in Combination with Intravenous Gemcitabine and Bevacizumab for Patients with Advanced Cancers and Predominant Liver Metastases

PubMed Central

Tsimberidou, Apostolia M.; Ye, Yang; Wheler, Jennifer; Naing, Aung; Hong, David; Nwosu, Uchechi; Hess, Kenneth R.; Wolff, Robert A.

2014-01-01

PURPOSE We conducted a Phase I clinical trial for patients with advanced cancer and predominant liver disease. EXPERIMENTAL DESIGN Patients were treated with HAI nab-paclitaxel (120-210 mg/m2; day 1); intravenous bevacizumab (10 mg/kg; day 1); and intravenous gemcitabine (600-800 mg/m2; days 1 and 8). A conventional “3 + 3” study design was used. RESULTS Fifty patients with advanced cancer and predominant liver metastases were treated (median age, 58 years; 27 women, 23 men; median number of prior therapies, 3 [range, 0-12]). The most common cancers were breast (n=9) and pancreatic (n=9). Overall, 264 cycles were administered (median/patient, 4; range, 1-17). No dose-limiting toxicities were noted during the escalation phase. On dose level 4, 3 patients were unable to receive gemcitabine on day 8 because of severe thrombocytopenia. Dose level 3 was selected as the maximum tolerated dose (HAI nab-paclitaxel 180 mg/m2 and intravenous gemcitabine 800 mg/m2 and bevacizumab 10 mg/kg); Thirty-two patients were treated in the expansion phase. The most common treatment-related toxicities were thrombocytopenia (n=17), neutropenia (n=10), and fatigue (n=12). Of 46 patients evaluable for response, 9 (20%) had a partial response [1] and 9 (20%) had stable disease for {greater than or equal to} 6 months. The median overall survival duration was 7.0 months (95% CI: 4, 22 months) and the median progression-free survival duration was 4.2 months (95% CI: 2.7, 8.6 months). CONCLUSIONS HAI nab-paclitaxel in combination with gemcitabine and bevacizumab was well tolerated and had antitumor activity in selected patients with advanced cancer and liver metastases. PMID:23377373

Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

PubMed

Popov, I P; Jelić, S B; Krivokapić, Z V; Jezdić, S D; Pesko, P M; Micev, M T; Babić, D R

2008-01-01

To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. Histologically confirmed measurable advanced gastric cancer, age < 72 yr, ECOG performance status 0-2, no prior chemo- and radiotherapy, adequate organ functions. EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.

Design and implementation of a head-and-neck phantom for system audit and verification of intensity-modulated radiation therapy.

PubMed

Webster, Gareth J; Hardy, Mark J; Rowbottom, Carl G; Mackay, Ranald I

2008-04-16

The head and neck is a challenging anatomic site for intensity-modulated radiation therapy (IMRT), requiring thorough testing of planning and treatment delivery systems. Ideally, the phantoms used should be anatomically realistic, have radiologic properties identical to those of the tissues concerned, and allow for the use of a variety of devices to verify dose and dose distribution in any target or normaltissue structure. A phantom that approaches the foregoing characteristics has been designed and built; its specific purpose is verification for IMRT treatments in the head-andneck region. This semi-anatomic phantom, HANK, is constructed of Perspex (Imperial Chemical Industries, London, U.K.) and provides for the insertion of heterogeneities simulating air cavities in a range of fixed positions. Chamber inserts are manufactured to incorporate either a standard thimble ionization chamber (0.125 cm3: PTW, Freiburg, Germany) or a smaller PinPoint chamber (0.015 cm3: PTW), and measurements can be made with either chamber in a range of positions throughout the phantom. Coronal films can also be acquired within the phantom, and additional solid blocks of Perspex allow for transverse films to be acquired within the head region. Initial studies using simple conventional head-and-neck plans established the reproducibility of the phantom and the measurement devices to within the setup uncertainty of +/- 0.5 mm. Subsequent verification of 9 clinical head-and-neck IMRT plans demonstrated the efficacy of the phantom in making a range of patient-specific dose measurements in regions of dosimetric and clinical interest. Agreement between measured values and those predicted by the Pinnacle3 treatment planning system (Philips Medical Systems, Andover, MA) was found to be generally good, with a mean error on the calculated dose to each point of +0.2% (range: -4.3% to +2.2%; n = 9) for the primary planning target volume (PTV), -0.1% (range: -1.5% to +2.0%; n = 8) for the nodal PTV, and +0.0% (range: -1.8% to +4.3%, n = 9) for the spinal cord. The suitability of the phantom for measuring combined dose distributions using radiographic film was also evaluated. The phantom has proved to be a valuable tool in the development and implementation of clinical head-and-neck IMRT, allowing for accurate verification of absolute dose and dose distributions in regions of clinical and dosimetric interest.

Integrated pharmacokinetics and pharmacodynamics of Ro 48-8684, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects.

PubMed

van Gerven, J M; Roncari, G; Schoemaker, R C; Massarella, J; Keesmaat, P; Kooyman, H; Heizmann, P; Zell, M; Cohen, A F; Dingemanse, J

1997-11-01

This study aimed to investigate the pharmacodynamics and pharmacokinetics of ascending doses of Ro 48-8684, compared with midazolam, in healthy subjects during first administration to man. The study was double-blind and five-way crossover (three ascending doses, placebo, fixed midazolam dose), performed in two groups of five males. Ro 48-8684 was infused in doses of 0.1-0.3-1 mg in the first group, and 1-3-10 mg in the second, with different infusion rates (expressed as mg min(-1)) among doses. Midazolam was infused at 0.1 mg(-1) kg. Infusions were stopped after 20 min or if sedation became too strong for proper performance of saccadic eye movements. Pharmacokinetics and pharmacodynamics and their relationships were evaluated as described in the companion article. Ro 48-8684 caused dose-dependent sedation. No serious adverse events occurred. The volume of distribution and clearance of Ro 48-8684 were larger than of midazolam (337+/-114 vs 50+/-121 and 2.4+/-0.5 vs 0.47+/-0.11 l min(-1), resp). The recovery of saccadic eye movements from equal levels of sedation was on average almost half an hour faster for Ro 48-8684 than for midazolam, with considerable interindividual differences (range 2, 55 min). The doses of Ro 48-8684 leading to the same clinical endpoint as midazolam were comparable, but the corresponding predicted effect compartment concentrations of Ro 48-8684 were on average 2.6 times lower (range 1.5, 4.9 times). The slope of the linear concentration-effect-relationship for saccadic peak velocity was on average 2.2 times steeper for 10 mg Ro 48-8684 than for midazolam (range 1.3, 3.3). The slope decreased on average 4.4-fold (range 1.6, 7.3 times), with doses of Ro 48-8684 increasing from 1 to 10 mg. The metabolite Ro 61-2466 had a longer half-life than the parent compound Ro 48-8684. The influence of this metabolite during prolonged administration should be further investigated. These results show that Ro 48-8684 has a considerably shorter duration of action than midazolam. There may be a reduction of sensitivity to Ro 48-8684 with repeated administration of rising doses due to as yet undetermined factors.

Volumetric modulated arc radiotherapy for esophageal cancer.

PubMed

Vivekanandan, Nagarajan; Sriram, Padmanaban; Kumar, S A Syam; Bhuvaneswari, Narayanan; Saranya, Kamalakannan

2012-01-01

A treatment planning study was performed to evaluate the performance of volumetric arc modulation with RapidArc (RA) against 3D conformal radiation therapy (3D-CRT) and conventional intensity-modulated radiation therapy (IMRT) techniques for esophageal cancer. Computed tomgraphy scans of 10 patients were included in the study. 3D-CRT, 4-field IMRT, and single-arc and double-arc RA plans were generated with the aim to spare organs at risk (OAR) and healthy tissue while enforcing highly conformal target coverage. The planning objective was to deliver 54 Gy to the planning target volume (PTV) in 30 fractions. Plans were evaluated based on target conformity and dose-volume histograms of organs at risk (lung, spinal cord, and heart). The monitor unit (MU) and treatment delivery time were also evaluated to measure the treatment efficiency. The IMRT plan improves target conformity and spares OAR when compared with 3D-CRT. Target conformity improved with RA plans compared with IMRT. The mean lung dose was similar in all techniques. However, RA plans showed a reduction in the volume of the lung irradiated at V(₂₀Gy) and V(₃₀Gy) dose levels (range, 4.62-17.98%) compared with IMRT plans. The mean dose and D(₃₅%) of heart for the RA plans were better than the IMRT by 0.5-5.8%. Mean V(₁₀Gy) and integral dose to healthy tissue were almost similar in all techniques. But RA plans resulted in a reduced low-level dose bath (15-20 Gy) in the range of 14-16% compared with IMRT plans. The average MU needed to deliver the prescribed dose by RA technique was reduced by 20-25% compared with IMRT technique. The preliminary study on RA for esophageal cancers showed improvements in sparing OAR and healthy tissue with reduced beam-on time, whereas only double-arc RA offered improved target coverage compared with IMRT and 3D-CRT plans. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-F-J-162: Is Bulky Electron Density Assignment Appropriatefor MRI-Only Based Treatment Planning for Lung Cancer?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prior, P; Chen, X; Johnstone, C

Purpose: To assess the appropriateness of bulky electron density assisment for MRI-only treatment planning for lung cancer via comparing dosimetric difference between MRI- and CT-based plans. Methods: Planning 4DCTs acquired for six representative lung cancer patients were used to generate CT-based IMRT plans. To avoid the effect of anatomic difference between CT and MRI, MRI-based plans were generated using CTs by forcing the relative electron density (rED) of organ specific values from ICRU report 46 and using the mean rED value of the internal target volume (ITV) of the patient for the ITV. Both CT and “MRI” plans were generatedmore » using a research planning system (Monaco, Elekta) employing Monte Carlo dose calculation the following dose-volume-parameters (DVPs): D99 – dose delivered to 99% of the ITV/PTV volume; D95; D5; D1; Vpd –volume receiving the prescription dose; V5 – volume of normal lung irradiated > 5 Gy; and V20. The percent point difference and dose difference was used for comparison for Vpd-V5-V20 and D99-D1, respectively. Four additional plans per patient were calculated with rEDITV = 0.6 and 1.0 and rEDlung = 0.1 and 0.5. Results: Noticeable differences in the ITV and PTV point doses and DVPs were observed. Variations in Vpd ranged from 0.0–6.4% and 0.32–18.3% for the ITV and PTV, respectively. The ITV and PTV variations in D99, D95, D5 and D1 were 0.15–3.2 Gy. The normal lung V5 & V20 variations were no larger than 1.9%. In some instances, varying the rEDITV between rEDmean, 0.6 and 1.0 resulted in D95 increases ranging from 3.9–6.3%. Uniform rED assignment on normal lung affected DVPs of ITV and PTV by 4.0–9.8% and 0.3–19.6%, respectively. Conclusion: The commonly-used uniform rED assignment in MRI-only based planning may not be appropriate for lung-cancer. A voxel based method, e.g. synthetic CT generated from MRI data, is required. This work was partially funded by Elekta, Inc.« less

Balanced propofol sedation administered by nonanesthesiologists: The first Italian experience

PubMed Central

Repici, Alessandro; Pagano, Nico; Hassan, Cesare; Carlino, Alessandra; Rando, Giacomo; Strangio, Giuseppe; Romeo, Fabio; Zullo, Angelo; Ferrara, Elisa; Vitetta, Eva; Ferreira, Daniel de Paula Pessoa; Danese, Silvio; Arosio, Massimo; Malesci, Alberto

2011-01-01

AIM: To assess the efficacy and safety of a balanced approach using midazolam in combination with propofol, administered by non-anesthesiologists, in a large series of diagnostic colonoscopies. METHODS: Consecutive patients undergoing diagnostic colonoscopy were sedated with a single dose of midazolam (0.05 mg/kg) and low-dose propofol (starter bolus of 0.5 mg/kg and repeated boluses of 10 to 20 mg). Induction time and deepest level of sedation, adverse and serious adverse events, as well as recovery times, were prospectively assessed. Cecal intubation and adenoma detection rates were also collected. RESULTS: Overall, 1593 eligible patients were included. The median dose of propofol administered was 70 mg (range: 40-120 mg), and the median dose of midazolam was 2.3 mg (range: 2-4 mg). Median induction time of sedation was 3 min (range: 1-4 min), and median recovery time was 23 min (range: 10-40 min). A moderate level of sedation was achieved in 1561 (98%) patients, whilst a deep sedation occurred in 32 (2%) cases. Transient oxygen desaturation requiring further oxygen supplementation occurred in 8 (0.46%; 95% CI: 0.2%-0.8%) patients. No serious adverse event was observed. Cecal intubation and adenoma detection rates were 93.5% and 23.4% (27.8% for male and 18.5% for female, subjects), respectively. CONCLUSION: A balanced sedation protocol provided a minimalization of the dose of propofol needed to target a moderate sedation for colonoscopy, resulting in a high safety profile for non-anesthesiologist propofol sedation. PMID:21987624

Bupropion Dose-Dependently Reverses Nicotine Withdrawal Deficits in Contextual Fear Conditioning

PubMed Central

Portugal, George S.; Gould, Thomas J.

2007-01-01

Bupropion, a norepinephrine and dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist, facilitates smoking cessation and reduces some symptoms of nicotine withdrawal. However, the effects of bupropion on nicotine withdrawal-associated deficits in learning remain unclear. The present study investigated whether bupropion has effects on contextual and cued fear conditioning following withdrawal from chronic nicotine or when administered alone. Bupropion was administered alone for a range of doses (2.5, 5, 10, 20 or 40 mg/kg), and dose-dependent impairments in contextual and cued fear conditioning were observed (20 or 40 mg/kg). Follow-up studies investigated if bupropion disrupted acquisition or expression of fear conditioning. Bupropion (40 mg/kg) administration on training day only produced deficits in contextual fear conditioning. Alternatively, bupropion (20 or 40 mg/kg) administration during testing dose-dependently produced deficits in contextual and cued fear conditioning. To test the effect of bupropion on nicotine withdrawal, mice were withdrawn from 12 days of chronic nicotine (6.3 mg/kg/day) or saline treatment. Withdrawal from chronic nicotine disrupted contextual fear conditioning; however, 5 mg/kg bupropion reversed this deficit. Overall, these results indicate that a low dose of bupropion can reverse nicotine withdrawal deficits in contextual fear conditioning, but that high doses of bupropion produce deficits in fear conditioning. PMID:17868796

Intensity-Modulated and 3D-Conformal Radiotherapy for Whole-Ventricular Irradiation as Compared With Conventional Whole-Brain Irradiation in the Management of Localized Central Nervous System Germ Cell Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Michael Jenwei, E-mail: michaelchen@einstein.b; Silva Santos, Adriana da; Sakuraba, Roberto Kenji

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a 'boost' to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluatedmore » at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment.« less

Pharmacokinetics and Pharmacodynamics of Twice Daily and Once Daily Regimens of Empagliflozin in Healthy Subjects.

PubMed

Macha, Sreeraj; Brand, Tobias; Meinicke, Thomas; Link, Jasmin; Broedl, Uli C

2015-08-01

This study was undertaken to compare the steady-state pharmacokinetic and pharmacodynamic properties of empagliflozin 5 mg twice daily (BID) and 10 mg once daily (QD) in healthy subjects. In an open-label, 2-way crossover study, subjects (n = 16) received empagliflozin 5 mg BID for 5 days and empagliflozin 10 mg QD for 5 days in a randomized order, with a washout period of ≥6 days between each treatment. The primary objective was the comparison of the overall exposure during a 24-hour period at steady state (AUC0-24,ss) for empagliflozin, based on standard bioequivalence criteria, with BID and QD dose regimens. The study population comprised 7 (43.8%) men and 9 (56.3%) women with a baseline median age of 38.0 years (range, 23-47 years) and a median body mass index of 23.3 kg/m(2) (range, 19.8-27.8 kg/m(2)). Based on standard bioequivalence criteria, there was no difference in the overall exposure of empagliflozin between BID and QD dose regimens (geometric mean ratio of AUC0-24,ss for empagliflozin 5 mg BID compared with empagliflozin 10 mg QD = 99.36%; 90% CI, 94.29-104.71). For empagliflozin 10 mg QD, mean (%CV) AUC during the dosing interval was 1900 nmol · h/L (20.6%), mean (%CV) Cmax,ss was 330 nmol/L (25.3%), and median (range) Tmax,ss was 1.0 hour (0.7-2.0 hours). For empagliflozin 5 mg BID, mean (%CV) AUC during the dosing interval was 1010 nmol · h/L (15.1%) and 867 nmol · h/L (18.6%) after the morning and evening dose, respectively, mean (%CV) Cmax,ss was 193 nmol/L (16.5%) and 120 nmol/L (21.0%), respectively, and median Tmax,ss was 1.0 hour (range, 0.7-2.0 hours) and 2.0 hours (range, 1.0-4.0 hours), respectively. The mean (%CV) cumulative amount of glucose excreted in urine during 24 hours was 52.1 g (32.1%) with empagliflozin 5 mg BID and 43.9 g (30.3%) with empagliflozin 10 mg QD. Adverse events were reported in six subjects (37.5%) receiving empagliflozin 5 mg BID and four (25.0%) receiving empagliflozin 10 mg QD. Headache was the most frequent AE. No severe, serious, or drug-related AEs were reported. There were no clinically relevant differences in pharmacokinetic or pharmacodynamic properties between BID and QD dose regimens of empagliflozin in healthy subjects. Both dose regimens were well tolerated. EU Clinical Trials Register (EudraCT) number: 2009-012524-90. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma.

PubMed

Chamberlain, Marc C; Johnston, Sandra K

2010-07-01

We conducted a prospective Phase II study of high-dose methotrexate (HD-MTX) and rituximab with deferred whole brain radiotherapy in patients with newly diagnosed B-cell primary central nervous system lymphoma with a primary objective of evaluating progression-free survival (PFS). Forty patients (25 men; 15 women), ages 18-93 years (median 61.5), were treated. All patients received biweekly HD-MTX/rituximab (8 g/m(2)/dose; 375 mg/m(2)/dose) for 4-6 cycles (induction) and following best radiographic response, with every 4 weeks HD-MTX (8 g/m(2)/dose) for 4 cycles (maintenance). Neurological and neuroradiographic evaluation were performed every 4 weeks during induction therapy and every 8 weeks during maintenance therapy. All patients were evaluable. A total of 303 cycles of HD-MTX (median 8 cycles; range 4-10) was administered. HD-MTX/rituximab-related toxicity included 16 grade 3 adverse events in 13 patients (32.5%). Following induction, 8 patients (20%) demonstrated progressive disease and discontinued therapy; 32 patients (80%) demonstrated a partial (8/40; 20%) or complete (24/40; 60%) radiographic response. At the conclusion of maintenance therapy (6-10 months of total therapy), 28 patients (70%) demonstrated either a partial (1/28) or complete (27/28) response. Overall, survival of these 28 patients ranged from 11 to 80 months (median 33.5). Survival in the entire cohort ranged from 6 to 80 months with an estimated median of 29 months. Overall, PFS ranged from 2 to 80 months (median 21.0). HD-MTX/rituximab and deferred radiotherapy demonstrated similar or better efficacy similar to other HD-MTX-only regimens and reduced time on therapy on average to 6 months.

High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma

PubMed Central

Chamberlain, Marc C.; Johnston, Sandra K.

2010-01-01

We conducted a prospective Phase II study of high-dose methotrexate (HD-MTX) and rituximab with deferred whole brain radiotherapy in patients with newly diagnosed B-cell primary central nervous system lymphoma with a primary objective of evaluating progression-free survival (PFS). Forty patients (25 men; 15 women), ages 18–93 years (median 61.5), were treated. All patients received biweekly HD-MTX/rituximab (8 g/m2/dose; 375 mg/m2/dose) for 4–6 cycles (induction) and following best radiographic response, with every 4 weeks HD-MTX (8 g/m2/dose) for 4 cycles (maintenance). Neurological and neuroradiographic evaluation were performed every 4 weeks during induction therapy and every 8 weeks during maintenance therapy. All patients were evaluable. A total of 303 cycles of HD-MTX (median 8 cycles; range 4–10) was administered. HD-MTX/rituximab-related toxicity included 16 grade 3 adverse events in 13 patients (32.5%). Following induction, 8 patients (20%) demonstrated progressive disease and discontinued therapy; 32 patients (80%) demonstrated a partial (8/40; 20%) or complete (24/40; 60%) radiographic response. At the conclusion of maintenance therapy (6–10 months of total therapy), 28 patients (70%) demonstrated either a partial (1/28) or complete (27/28) response. Overall, survival of these 28 patients ranged from 11 to 80 months (median 33.5). Survival in the entire cohort ranged from 6 to 80 months with an estimated median of 29 months. Overall, PFS ranged from 2 to 80 months (median 21.0). HD-MTX/rituximab and deferred radiotherapy demonstrated similar or better efficacy similar to other HD-MTX-only regimens and reduced time on therapy on average to 6 months. PMID:20511181

Threshold dose for peripheral neuropathy following intraoperative radiotherapy (IORT) in a large animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinsella, T.J.; DeLuca, A.M.; Barnes, M.

1991-04-01

Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers andmore » perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.« less

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique.

PubMed

Gandhi, Diksha; Crotty, Dominic J; Stevens, Grant M; Schmidt, Taly Gilat

2015-11-01

This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings. Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%-20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.

Patient-specific quality assurance for the delivery of (60)Co intensity modulated radiation therapy subject to a 0.35-T lateral magnetic field.

PubMed

Li, H Harold; Rodriguez, Vivian L; Green, Olga L; Hu, Yanle; Kashani, Rojano; Wooten, H Omar; Yang, Deshan; Mutic, Sasa

2015-01-01

This work describes a patient-specific dosimetry quality assurance (QA) program for intensity modulated radiation therapy (IMRT) using ViewRay, the first commercial magnetic resonance imaging-guided RT device. The program consisted of: (1) a 1-dimensional multipoint ionization chamber measurement using a customized 15-cm(3) cube-shaped phantom; (2) 2-dimensional (2D) radiographic film measurement using a 30- × 30- × 20-cm(3) phantom with multiple inserted ionization chambers; (3) quasi-3D diode array (ArcCHECK) measurement with a centrally inserted ionization chamber; (4) 2D fluence verification using machine delivery log files; and (5) 3D Monte Carlo (MC) dose reconstruction with machine delivery files and phantom CT. Ionization chamber measurements agreed well with treatment planning system (TPS)-computed doses in all phantom geometries where the mean ± SD difference was 0.0% ± 1.3% (n=102; range, -3.0%-2.9%). Film measurements also showed excellent agreement with the TPS-computed 2D dose distributions where the mean passing rate using 3% relative/3 mm gamma criteria was 94.6% ± 3.4% (n=30; range, 87.4%-100%). For ArcCHECK measurements, the mean ± SD passing rate using 3% relative/3 mm gamma criteria was 98.9% ± 1.1% (n=34; range, 95.8%-100%). 2D fluence maps with a resolution of 1 × 1 mm(2) showed 100% passing rates for all plan deliveries (n=34). The MC reconstructed doses to the phantom agreed well with planned 3D doses where the mean passing rate using 3% absolute/3 mm gamma criteria was 99.0% ± 1.0% (n=18; range, 97.0%-100%), demonstrating the feasibility of evaluating the QA results in the patient geometry. We developed a dosimetry program for ViewRay's patient-specific IMRT QA. The methodology will be useful for other ViewRay users. The QA results presented here can assist the RT community to establish appropriate tolerance and action limits for ViewRay's IMRT QA. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiation optic neuropathy after megavoltage external-beam irradiation: Analysis of time-dose factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parsons, J.T.; Bova, F.J.; Million, R.R.

1994-11-15

To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 andmore » 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of <59 Gy. Among nerves that received doses of {ge} 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic compared with 47% when given in fraction sizes {ge}1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation. 32 refs., 5 figs., 5 tabs.« less

Internal dose assessment of 210Po using biokinetic modeling and urinary excretion measurement

PubMed Central

Gerstmann, Udo; Giussani, Augusto; Oeh, Uwe; Paretzke, Herwig G.

2007-01-01

The mysterious death of Mr. Alexander Litvinenko who was most possibly poisoned by Polonium-210 (210Po) in November 2006 in London attracted the attention of the public to the kinetics, dosimetry and the risk of this high radiotoxic isotope in the human body. In the present paper, the urinary excretion of seven persons who were possibly exposed to traces of 210Po was monitored. The values measured in the GSF Radioanalytical Laboratory are in the range of natural background concentration. To assess the effective dose received by those persons, the time-dependence of the organ equivalent dose and the effective dose after acute ingestion and inhalation of 210Po were calculated using the biokinetic model for polonium (Po) recommended by the International Commission on Radiological Protection (ICRP) and the one recently published by Leggett and Eckerman (L&E). The daily urinary excretion to effective dose conversion factors for ingestion and inhalation were evaluated based on the ICRP and L&E models for members of the public. The ingestion (inhalation) effective dose per unit intake integrated over one day is 1.7 × 10−8 (1.4 × 10−7) Sv Bq−1, 2.0 × 10−7 (9.6 × 10−7) Sv Bq−1 over 10 days, 5.2 × 10−7 (2.0 × 10−6) Sv Bq−1 over 30 days and 1.0 × 10−6 (3.0 × 10−6) Sv Bq−1 over 100 days. The daily urinary excretions after acute ingestion (inhalation) of 1 Bq of 210Po are 1.1 × 10−3 (1.0 × 10−4) on day 1, 2.0 × 10−3 (1.9 × 10−4) on day 10, 1.3 × 10−3 (1.7 × 10−4) on day 30 and 3.6 × 10−4 (8.3 × 10−5) Bq d−1 on day 100, respectively. The resulting committed effective doses range from 2.1 × 10−3 to 1.7 × 10−2 mSv by an assumption of ingestion and from 5.5 × 10−2 to 4.5 × 10−1 mSv by inhalation. For the case of Mr. Litvinenko, the mean organ absorbed dose as a function of time was calculated using both the above stated models. The red bone marrow, the kidneys and the liver were considered as the critical organs. Assuming a value of lethal absorbed dose of 5 Gy to the bone marrow, 6 Gy to the kidneys and 8 Gy to the liver, the amount of 210Po which Mr. Litvinenko might have ingested is therefore estimated to range from 27 to 1,408 MBq, i.e 0.2–8.5 μg, depending on the modality of intake and on different assumptions about blood absorption. PMID:17899149

Chromosome translocations in T. scripta: the dose-rate effect and in vivo lymphocyte radiation response.

PubMed

Ulsh, B A; Whicker, F W; Congdon, J D; Bedford, J S; Hinton, T G

2001-01-01

Using a whole-chromosome FISH painting probe we previously developed for chromosome 1 of the yellow-bellied slider turtle (Trachemys scripta), we investigated the dose-rate effect for radiation-induced symmetrical translocations in T. scripta fibroblasts and lymphocytes. The dose rate below which no reduction in effect per unit dose is observed with further dose protraction was approximately 23 cGy h(-1). We estimated the whole-genome spontaneous background level of complete, apparently simple symmetrical translocations in T. scripta lymphocytes to be approximately 1.20 x 10(-3)/cell projected from aberrations occurring in chromosome 1. Similar spontaneous background levels reported for humans are some 6- to 25-fold higher, ranging from about 6 x 10(-3) to 3.4 x 10(-2) per cell. This relatively low background level for turtles would be a significant advantage for resolution of effects at low doses and dose rates. We also chronically irradiated turtles over a range of doses from 0-8 Gy delivered at approximately 5.5 cGy h(-1) and constructed a lymphocyte dose-response curve for complete, apparently simple symmetrical translocations suitable for use with animals chronically exposed to radiation in contaminated environments. The best-fitting calibration curve (not constrained through the zero dose estimate) was of the form Y(as) = c + aD + bD(2), where Y(as) was the number of apparently simple symmetrical translocations per cell, D was the dose (Gy), a = (0.0058 +/- 0.0009), b = (-0.00033 +/- 0.00011), and c = (0.0015 +/- 0.0013). With additional whole-chromosome probes to improve sensitivity, environmental biodosimetry using stable chromosome translocations could provide a practical and genetically relevant measurement end point for ecological risk assessments and biomonitoring programs.

Effective dose assessment in the maxillofacial region using thermoluminescent (TLD) and metal oxide semiconductor field-effect transistor (MOSFET) dosemeters: a comparative study.

PubMed

Koivisto, J; Schulze, D; Wolff, J; Rottke, D

2014-01-01

The objective of this study was to compare the performance of metal oxide semiconductor field-effect transistor (MOSFET) technology dosemeters with thermoluminescent dosemeters (TLDs) (TLD 100; Thermo Fisher Scientific, Waltham, MA) in the maxillofacial area. Organ and effective dose measurements were performed using 40 TLD and 20 MOSFET dosemeters that were alternately placed in 20 different locations in 1 anthropomorphic RANDO(®) head phantom (the Phantom Laboratory, Salem, NY). The phantom was exposed to four different CBCT default maxillofacial protocols using small (4 × 5 cm) to full face (20 × 17 cm) fields of view (FOVs). The TLD effective doses ranged between 7.0 and 158.0 µSv and the MOSFET doses between 6.1 and 175.0 µSv. The MOSFET and TLD effective doses acquired using four different (FOV) protocols were as follows: face maxillofacial (FOV 20 × 17 cm) (MOSFET, 83.4 µSv; TLD, 87.6 µSv; -5%); teeth, upper jaw (FOV, 8.5 × 5.0 cm) (MOSFET, 6.1 µSv; TLD, 7.0 µSv; -14%); tooth, mandible and left molar (FOV, 4 × 5 cm) (MOSFET, 10.3 µSv; TLD, 12.3 µSv; -16%) and teeth, both jaws (FOV, 10 × 10 cm) (MOSFET, 175 µSv; TLD, 158 µSv; +11%). The largest variation in organ and effective dose was recorded in the small FOV protocols. Taking into account the uncertainties of both measurement methods and the results of the statistical analysis, the effective doses acquired using MOSFET dosemeters were found to be in good agreement with those obtained using TLD dosemeters. The MOSFET dosemeters constitute a feasible alternative for TLDs for the effective dose assessment of CBCT devices in the maxillofacial region.

High dose vitamin K3 infusion in advanced hepatocellular carcinoma.

PubMed

Sarin, Shiv K; Kumar, Manoj; Garg, Sanjay; Hissar, Syed; Pandey, Chandana; Sharma, Barjesh C

2006-09-01

The survival of patients with unresectable advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is dismal. Current therapeutic options have limited efficacy. Vitamin K has been shown to have antitumor effect on HCC cells both in cell lines and patients with advanced HCC. The aim of this study was to assess the clinical efficacy of high dose vitamin K3 in the treatment of advanced HCC with portal vein thrombosis. Forty-two consecutive patients with advanced HCC (Stage C according to BCLC staging system) with portal vein thrombosis were randomized into two groups: (i) high dose vitamin K3 (n = 23); and (ii) placebo (n = 19). The vitamin K3 was administered by i.v. infusion of 50 mg/day with daily increase of dose by 50 mg for 6 days, followed by 20 mg i.m. twice daily for 2 weeks. Of the 23 patients treated with vitamin K, one (4.3%) achieved complete response and three (13%) partial response, for a total of four (17.4%) objective responders overall. The overall mean survival was 8.9 +/- 8.8 months (median: 6; range 1-37 months) in the vitamin K group and 6.8 +/- 5.3 months (median: 5; range 1.5-21 months) in the placebo group (P = 0.552). The mean duration of survival was longer in patients in the vitamin K group who achieved objective response (22.5 +/- 12.2; median: 21; range 11-37 months) as compared to patients not achieving objective response (6.1 +/- 4.6; median: 5; range 1-16 months) (P = 0.0.002). Portal vein thrombosis resolved with complete patency in one (4.35%) patient. Treatment with high dose vitamin K produces objective response in 17% patients with improved survival in patients achieving objective response; however, it does not affect the overall survival.

Response of murine tumours to combinations of CCNU with misonidazole and other radiation sensitizers.

PubMed Central

Siemann, D. W.

1982-01-01

The effect of combinations of the conventional chemotherapeutic agent 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and nitroimidazole radiation sensitizers was evaluated in female C3H mice. Tumour response to single-agent or combination therapy was assessed in a tumour growth-delay assay. In the KHT sarcoma the simultaneous addition of misonidazole (MISO) was found to increase significantly the tumour growth delay resulting from CCNU treatment. The observed enhancement ratios (ER) increased with MISO dose, and ranged from 1.3 to 1.9 for sensitizer doses of 0.25-1.0 mg/g. The combination of CCNU and 1.0 or 0.5 mg/g MISO in the RIF-1 tumour or the MT-1 tumour produced ERs of approximately 2.0 and approximately 1.5 respectively. In the KHT sarcoma a series of other nitroimidazole sensitizers, including Ro-05-9963, SR-2555, SR-2508 and metronidazole (METRO), were also evaluated at equimolar doses (5 mmol/kg) in combination with a 20mg/kg dose of CCNU. Unlike MISO, these compounds in general failed to enhance the CCNU cytotoxicity in this tumour model. However, SR-2508 did enhance the response of the RIF-1 tumour to large single doses of CCNU, though not as much as MISO. Normal-tissue toxicity was determined using peripheral white blood cell (WBC) counts 3 days after treatment. CCNU doses of 10-50 mg/kg given either alone or in simultaneous combination with 0.5 or 1.0 mg/g MISO were studied. WBC toxicity increased with CCNU dose, but the addition of MISO at either dose did not significantly enhance this normal-tissue toxicity. PMID:6460517

Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms.

PubMed

Koivisto, Juha H; Wolff, Jan E; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-07-08

The aims of this study were to characterize reinforced metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low-dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50-90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point-dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k = 2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low-dose limit. The sensitivity was 3.09 ± 0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was -8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD-comparable low-dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the sensitivity is too low.

Dosimetric Factors and Toxicity in Highly Conformal Thoracic Reirradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Binkley, Michael S.; Hiniker, Susan M.; Chaudhuri, Aadel

Purpose: We determined cumulative dose to critical structures, rates of toxicity, and outcomes following thoracic reirradiation. Methods and Materials: We retrospectively reviewed our institutional database for patients treated between 2008 and 2014, who received thoracic reirradiation with overlap of 25% prescribed isodose lines. Patients received courses of hyperfractionated (n=5), hypofractionated (n=5), conventionally fractionated (n=21), or stereotactic ablative radiation therapy (n=51). Doses to critical structures were converted to biologically effective dose, expressed as 2 Gy per fraction equivalent dose (EQD2; α/β = 2 for spinal cord; α/β = 3 for other critical structures). Results: We identified 82 courses (44 for retreatment) in 38 patients reirradiated atmore » a median 16 months (range: 1-71 months) following initial RT. Median follow-up was 17 months (range: 3-57 months). Twelve- and 24-month overall survival rates were 79.6% and 57.3%, respectively. Eighteen patients received reirradiation for locoregionally recurrent non-small cell lung cancer with 12-month rates of local failure and regional recurrence and distant metastases rates of 13.5%, 8.1%, and 15.6%, respectively. Critical structures receiving ≥75 Gy EQD2 included spinal cord (1 cm{sup 3}; n=1), esophagus (1 cm{sup 3}; n=10), trachea (1 cm{sup 3}; n=11), heart (1 cm{sup 3}; n=9), aorta (1 cm{sup 3}; n=16), superior vena cava (1 cm{sup 3}; n=12), brachial plexus (0.2 cm{sup 3}; n=2), vagus nerve (0.2 cm{sup 3}; n=7), sympathetic trunk (0.2 cm{sup 3}; n=4), chest wall (30 cm{sup 3}; n=12), and proximal bronchial tree (1 cm{sup 3}; n=17). Cumulative dose-volume (D cm{sup 3}) toxicity following reirradiation data included esophagitis grade ≥2 (n=3, D1 cm{sup 3} range: 41.0-100.6 Gy), chest wall grade ≥2 (n=4; D30 cm{sup 3} range: 35.0-117.2 Gy), lung grade 2 (n=7; V20{sub combined-lung} range: 4.7%-21.7%), vocal cord paralysis (n=2; vagus nerve D0.2 cm{sup 3} range: 207.5-302.2 Gy), brachial plexopathy (n=1; D0.2 cm{sup 3} = 242.5 Gy), and Horner's syndrome (n=1; sympathetic trunk D0.2 cm{sup 3} = 130.8 Gy). No grade ≥4 toxicity was observed. Conclusions: Overlapping courses of reirradiation can be safely delivered with acceptable toxicity. Some toxicities occurred acutely at doses considered safe for a single course of therapy (esophagus). We observed rib fracture, brachial plexopathy, and Horner's syndrome for patients receiving high cumulative doses to corresponding critical structures.« less

Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chadha, Awalpreet S.; Liu, Guan; Chen, Hsiang-Chun

2017-02-01

Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gymore » (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, M; Choi, E; Chuong, M

Purpose: To evaluate weather the current radiobiological models can predict the normal liver complications of radioactive Yttrium-90 ({sup 90}Y) selective-internal-radiation-treatment (SIRT) for metastatic liver lesions based on the post-infusion {sup 90}Y PET images. Methods: A total of 20 patients with metastatic liver tumors treated with SIRT that received a post-infusion {sup 90}Y-PET/CT scan were analyzed in this work. The 3D activity distribution of the PET images was converted into a 3D dose distribution via a kernel convolution process. The physical dose distribution was converted into the equivalent dose (EQ2) delivered at 2 Gy based on the linear-quadratic (LQ) model consideringmore » the dose rate effect. The biological endpoint of this work was radiation-induce liver disease (RILD). The NTCPs were calculated with four different repair-times (T1/2-Liver-Repair= 0,0.5,1.0,2.0 hr) and three published NTCP models (Lyman-external-RT, Lyman 90Y-HCC-SIRT, parallel model) were compared to the incidence of RILD of the recruited patients to evaluate their ability of outcome prediction. Results: The mean normal liver physical dose (avg. 51.9 Gy, range 31.9–69.8 Gy) is higher than the suggested liver dose constraint for external beam treatment (∼30 Gy). However, none of the patients in our study developed RILD after the SIRT. The estimated probability of ‘no patient developing RILD’ obtained from the two Lyman models are 46.3% to 48.3% (T1/2-Liver-Repair= 0hr) and <1% for all other repair times. For the parallel model, the estimated probability is 97.3% (0hr), 51.7% (0.5hr), 2.0% (1.0hr) and <1% (2.0hr). Conclusion: Molecular-images providing the distribution of {sup 90}Y enable the dose-volume based dose/outcome analysis for SIRT. Current NTCP models fail to predict RILD complications in our patient population, unless a very short repair-time for the liver is assumed. The discrepancy between the Lyman {sup 90}Y-HCC-SIRT model predicted and the clinically observed outcomes further demonstrates the need of an NTCP model specific to the metastatic liver SIRT.« less

Towards the definition of Institutional diagnostic reference levels in paediatric interventional cardiology procedures in Greece.

PubMed

Kottou, S; Kollaros, N; Plemmenos, C; Mastorakou, I; Apostolopoulou, S C; Tsapaki, V

2018-02-01

This study aimed to evaluate paediatric radiation doses in a dedicated cardiology hospital, with the objective of characterising patterns in dose variation. The ultimate purpose was to define Local (Institutional) Diagnostic Reference Levels (LDRLs) for different types of paediatric cardiac interventional procedures (IC), according to patient age. From a total of 710 cases performed during three consecutive years, by operators with more than 15 years of experience, the age was noted in only 477 IC procedures. The median values obtained for Fluoroscopy Time (FT), Number of Frames (N) and Kerma Area Product (P KA ) by age range were 5.8 min, 1322 and 2.0 Gy.cm 2 for <1 y; 6.5 min, 1403 and 3.0 Gy.cm 2 for 1 to <5 y; 5.9 min, 950 and 7.0 Gy.cm 2 for 5 to <10 y; 5.7 min, 940 and 14.0 Gy.cm 2 for 10 to <16 y, respectively. A large range of patient dose data is observed, depending greatly on procedure type and patient age. In all age groups the range of median FT, N and P KA values was 3.1-15.8 min, 579-1779 and 1.0-20.8 Gy.cm 2 respectively. Consequently, the definition of LDRLs presents challenges mainly due to the multiple clinical and technical factors affecting the outcome. On the other hand the lack of paediatric IC DRLs makes the identification of good practices more difficult. A consensus is needed on IC procedures nomenclature and grouping in order to allow a common assessment and comparison of doses. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Biological and dosimetric characterisation of spatially fractionated proton minibeams

NASA Astrophysics Data System (ADS)

Meyer, Juergen; Stewart, Robert D.; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-12-01

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Biological and dosimetric characterisation of spatially fractionated proton minibeams.

PubMed

Meyer, Juergen; Stewart, Robert D; Smith, Daniel; Eagle, James; Lee, Eunsin; Cao, Ning; Ford, Eric; Hashemian, Reza; Schuemann, Jan; Saini, Jatinder; Marsh, Steve; Emery, Robert; Dorman, Eric; Schwartz, Jeff; Sandison, George

2017-11-21

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Real-Time Patient and Staff Radiation Dose Monitoring in IR Practice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sailer, Anna M., E-mail: karmanna@stanford.edu; Paulis, Leonie, E-mail: leonie.paulis@mumc.nl; Vergoossen, Laura

PurposeKnowledge of medical radiation exposure permits application of radiation protection principles. In our center, the first dedicated real-time, automated patient and staff dose monitoring system (DoseWise Portal, Philips Healthcare) was installed. Aim of this study was to obtain insight in the procedural and occupational doses.Materials and MethodsAll interventional radiologists, vascular surgeons, and technicians wore personal dose meters (PDMs, DoseAware, Philips Healthcare). The dose monitoring system simultaneously registered for each procedure dose-related data as the dose area product (DAP) and effective staff dose (E) from PDMs. Use and type of shielding were recorded separately. All procedures were analyzed according to proceduremore » type; these included among others cerebral interventions (n = 112), iliac and/or caval venous recanalization procedures (n = 68), endovascular aortic repair procedures (n = 63), biliary duct interventions (n = 58), and percutaneous gastrostomy procedure (n = 28).ResultsMedian (±IQR) DAP doses ranged from 2.0 (0.8–3.1) (percutaneous gastrostomy) to 84 (53–147) Gy cm{sup 2} (aortic repair procedures). Median (±IQR) first operator doses ranged from 1.6 (1.1–5.0) μSv to 33.4 (12.1–125.0) for these procedures, respectively. The relative exposure, determined as first operator dose normalized to procedural DAP, ranged from 1.9 in biliary interventions to 0.1 μSv/Gy cm{sup 2} in cerebral interventions, indicating large variation in staff dose per unit DAP among the procedure types.ConclusionReal-time dose monitoring was able to identify the types of interventions with either an absolute or relatively high staff dose, and may allow for specific optimization of radiation protection.« less

A phase I study of docetaxel as a radio-sensitizer for locally advanced squamous cell cervical cancer.

PubMed

Alvarez, Edwin A; Wolfson, Aaron H; Pearson, J Matt; Crisp, Meredith P; Mendez, Luis E; Lambrou, Nicholas C; Lucci, Joseph A

2009-05-01

This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy (RT) for the primary treatment of locally advanced squamous cell carcinoma of the cervix. Eligible patients included those with locally advanced squamous cell cervical cancer without para-aortic lymph node involvement. Docetaxel dose levels were 20 mg/m(2), 30 mg/m(2) and 40 mg/m(2) given intravenously weekly for 6 cycles. Three patients were to be treated at each dose level and 6 to receive the MTD. Fifteen patients completed 4-6 cycles of chemotherapy. One of three patients experienced 2 delayed grade 3 severe adverse events (SAE) at the 20 mg/m(2) dose level consisting of colonic and ureteral obstruction. At the 30 mg/m(2) dose level, 1/4 patients had a probable treatment-related celiotomy due to obstipation and a necrotic tumor. Of the 8 patients treated at the 40 mg/m(2) dose level, 1 experienced grade 3 pneumonitis, likely treatment related. Overall, 10/15 (67%) experienced grade 1 or 2 diarrhea, 6 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. 10 of 16 patients (67%) had no evidence of disease with follow-up ranging from 10-33 months (average 23 months). The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for locally advanced squamous cell carcinoma of the cervix is 40 mg/m(2).

Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.

PubMed

Mease, Philip; Hall, Stephen; FitzGerald, Oliver; van der Heijde, Désirée; Merola, Joseph F; Avila-Zapata, Francisco; Cieślak, Dorota; Graham, Daniela; Wang, Cunshan; Menon, Sujatha; Hendrikx, Thijs; Kanik, Keith S

2017-10-19

Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs). In this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53). Placebo groups were pooled for analyses up to month 3. Primary end points were the proportion of patients who had an American College of Rheumatology 20 (ACR20) response (≥20% improvement from baseline in the number of tender and swollen joints and at least three of five other important domains) at month 3 and the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score (scores range from 0 to 3, with higher scores indicating greater disability) at month 3. ACR20 response rates at month 3 were 50% in the 5-mg tofacitinib group and 61% in the 10-mg tofacitinib group, as compared with 33% in the placebo group (P=0.01 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the rate was 52% in the adalimumab group. The mean change in the HAQ-DI score was -0.35 in the 5-mg tofacitinib group and -0.40 in the 10-mg tofacitinib group, as compared with -0.18 in the placebo group (P=0.006 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the score change was -0.38 in the adalimumab group. The rate of adverse events through month 12 was 66% in the 5-mg tofacitinib group, 71% in the 10-mg tofacitinib group, 72% in the adalimumab group, 69% in the placebo group that switched to the 5-mg tofacitinib dose, and 64% in the placebo group that switched to the 10-mg tofacitinib dose. There were four cases of cancer, three serious infections, and four cases of herpes zoster in patients who received tofacitinib during the trial. The efficacy of tofacitinib was superior to that of placebo at month 3 in patients with psoriatic arthritis who had previously had an inadequate response to conventional synthetic DMARDs. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Broaden ClinicalTrials.gov number, NCT01877668 .).

Validation of a method for in vivo 3D dose reconstruction for IMRT and VMAT treatments using on-treatment EPID images and a model-based forward-calculation algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Uytven, Eric, E-mail: eric.vanuytven@cancercare.mb.ca; Van Beek, Timothy; McCowan, Peter M.

2015-12-15

Purpose: Radiation treatments are trending toward delivering higher doses per fraction under stereotactic radiosurgery and hypofractionated treatment regimens. There is a need for accurate 3D in vivo patient dose verification using electronic portal imaging device (EPID) measurements. This work presents a model-based technique to compute full three-dimensional patient dose reconstructed from on-treatment EPID portal images (i.e., transmission images). Methods: EPID dose is converted to incident fluence entering the patient using a series of steps which include converting measured EPID dose to fluence at the detector plane and then back-projecting the primary source component of the EPID fluence upstream of themore » patient. Incident fluence is then recombined with predicted extra-focal fluence and used to calculate 3D patient dose via a collapsed-cone convolution method. This method is implemented in an iterative manner, although in practice it provides accurate results in a single iteration. The robustness of the dose reconstruction technique is demonstrated with several simple slab phantom and nine anthropomorphic phantom cases. Prostate, head and neck, and lung treatments are all included as well as a range of delivery techniques including VMAT and dynamic intensity modulated radiation therapy (IMRT). Results: Results indicate that the patient dose reconstruction algorithm compares well with treatment planning system computed doses for controlled test situations. For simple phantom and square field tests, agreement was excellent with a 2%/2 mm 3D chi pass rate ≥98.9%. On anthropomorphic phantoms, the 2%/2 mm 3D chi pass rates ranged from 79.9% to 99.9% in the planning target volume (PTV) region and 96.5% to 100% in the low dose region (>20% of prescription, excluding PTV and skin build-up region). Conclusions: An algorithm to reconstruct delivered patient 3D doses from EPID exit dosimetry measurements was presented. The method was applied to phantom and patient data sets, as well as for dynamic IMRT and VMAT delivery techniques. Results indicate that the EPID dose reconstruction algorithm presented in this work is suitable for clinical implementation.« less

Analysis of Dose at the Site of Second Tumor Formation After Radiotherapy to the Central Nervous System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galloway, Thomas J.; University of Florida Proton Therapy Institute, Jacksonville, FL; Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org

Purpose: Second tumors are an uncommon complication of multimodality treatment of childhood cancer. The present analysis attempted to correlate the dose received as a component of primary treatment and the site of the eventual development of a second tumor. Methods and Materials: We retrospectively identified 16 patients who had received radiotherapy to sites in the craniospinal axis and subsequently developed a second tumor. We compared the historical fields and port films of the primary treatment with the modern imaging of the second tumor locations. We classified the location of the second tumors as follows: in the boost field; marginal tomore » the boost field, but in a whole-brain field; in a whole-brain field; marginal to the whole brain/primary treatment field; and distant to the field. We divided the dose received into 3 broad categories: high dose (>45 Gy), moderate dose (20-36 Gy), and low dose (<20 Gy). Results: The most common location of the second tumor was in the whole brain field (57%) and in the moderate-dose range (81%). Conclusions: Our data contradict previous publications that suggested that most second tumors develop in tissues that receive a low radiation dose. Almost all the second tumors in our series occurred in tissue within a target volume in the cranium that had received a moderate dose (20-36 Gy). These findings suggest that a major decrease in the brain volume that receives a moderate radiation dose is the only way to substantially decrease the second tumor rate after central nervous system radiotherapy.« less

First radon measurements and occupational exposure assessments in underground geodynamic laboratory the Polish Academy of Sciences Space Research Centre in Książ Castle (SW Poland).

PubMed

Fijałkowska-Lichwa, Lidia; Przylibski, Tadeusz A

2016-12-01

The article presents the results of the first radon activity concentration measurements conducted continuously between 17 th May 2014 and 16 th May 2015 in the underground geodynamic laboratory of the Polish Academy of Sciences Space Research Centre in Książ. The data were registered with the use of three Polish semiconductor SRDN-3 detectors located the closest (SRDN-3 No. 6) to and the furthest (SRDN-3 No. 3) from the facility entrance, and in the fault zone (SRDN-3 No. 4). The study was conducted to characterize the radon behaviour and check it possibility to use with reference to long- and short-term variations of radon activity concentration observed in sedimentary rocks strongly fractured and intersected by systems of multiple faults, for integrated comparative assessments of changes in local orogen kinetics. The values of radon activity concentration in the underground geodynamic laboratory of the Polish Academy of Sciences (PAN) Space Research Centre in Książ undergo changes of a distinctly seasonal character. The highest values of radon activity concentration are recorded from late spring (May/June) to early autumn (October), and the lowest - from November to April. Radon activity concentrations varied depending on the location of measurement points. Between late spring and autumn they ranged from 800 Bq·m -3 to 1200 Bq·m -3 , and even 3200 Bq·m -3 in the fault zone. Between November and April, values of radon activity concentration are lower, ranging from 500 Bq·m -3 to 1000 Bq·m -3 and 2700 Bq·m -3 in the fault zone. The values of radon activity concentration recorded in the studied facility did not undergo short-term changes in either the whole annual measuring cycle or any of its months. Effective doses received by people staying in the underground laboratory range from 0.001 mSv/h to 0.012 mSv/h. The mean annual effective dose, depending on the measurement site, equals 1 or is slightly higher than 10 mSv/year, while the maximum dose exceeds 20 mSv/year. The estimated annual effective doses are comparable to the standard value of 20 mSv/year defined by Polish law for people employed in the conditions of radiation exposure. They are also in the range of annual effective dose value (8 mSv/year) recommended in workplaces by International Commission on Radiation Protection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occupational dose in interventional radiology procedures.

PubMed

Chida, Koichi; Kaga, Yuji; Haga, Yoshihiro; Kataoka, Nozomi; Kumasaka, Eriko; Meguro, Taiichiro; Zuguchi, Masayuki

2013-01-01

Interventional radiology tends to involve long procedures (i.e., long fluoroscopic times). Therefore, radiation protection for interventional radiology staff is an important issue. This study describes the occupational radiation dose for interventional radiology staff, especially nurses, to clarify the present annual dose level for interventional radiology nurses. We compared the annual occupational dose (effective dose and dose equivalent) among interventional radiology staff in a hospital where 6606 catheterization procedures are performed annually. The annual occupational doses of 18 physicians, seven nurses, and eight radiologic technologists were recorded using two monitoring badges, one worn over and one under their lead aprons. The annual mean ± SD effective dose (range) to the physicians, nurses, and radiologic technologists using two badges was 3.00 ± 1.50 (0.84-6.17), 1.34 ± 0.55 (0.70-2.20), and 0.60 ± 0.48 (0.02-1.43) mSv/y, respectively. Similarly, the annual mean ± SD dose equivalent range was 19.84 ± 12.45 (7.0-48.5), 4.73 ± 0.72 (3.9-6.2), and 1.30 ± 1.00 (0.2-2.7) mSv/y, respectively. The mean ± SD effective dose for the physicians was 1.02 ± 0.74 and 3.00 ± 1.50 mSv/y for the one- and two-badge methods, respectively (p < 0.001). Similarly, the mean ± SD effective dose for the nurses (p = 0.186) and radiologic technologists (p = 0.726) tended to be lower using the one-badge method. The annual occupational dose for interventional radiology staff was in the order physicians > nurses > radiologic technologists. The occupational dose determined using one badge under the apron was far lower than the dose obtained with two badges in both physicians and nonphysicians. To evaluate the occupational dose correctly, we recommend use of two monitoring badges to evaluate interventional radiology nurses as well as physicians.

Characterization of optically stimulated luminescent dosimeters, OSLDs, for clinical dosimetric measurements.

PubMed

Jursinic, Paul A

2007-12-01

Optically stimulated luminescent dosimeters, OSLDs, are plastic disks infused with aluminum oxide doped with carbon (Al2O3 : C). These disks are encased in a light-tight plastic holder. Crystals of Al2O3 : C when exposed to ionizing radiation store energy that is released as luminescence (420 nm) when the OSLD is illuminated with stimulation light (540 nm). The intensity of the luminescence depends on the dose absorbed by the OSLD and the intensity of the stimulation light. OSLDs used in this work were InLight/OSL Dot dosimeters, which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). The following are dosimetric properties of the OSLD that were determined: After a single irradiation, repeated readings cause the signal to decrease by 0.05% per reading; the signal could be discharged by greater than 98% by illuminating them for more than 45 s with a 150 W tungsten-halogen light; after irradiation there was a transient signal that decayed with a 0.8 min halftime; after the transient signal decay the signal was stable for days; repeated irradiations and readings of an individual OSLD gave a signal with a coefficient of variation of 0.6%; the dose sensitivity of OSLDs from a batch of detectors has a coefficient of variation of 0.9%, response was linear with absorbed dose over a test range of 1-300 cGy; above 300 cGy a small supra-linear behavior occurs; there was no dose-per-pulse dependence over a 388-fold range; there was no dependence on radiation energy or mode for 6 and 15 MV x rays and 6-20 MeV electrons; for Ir-192 gamma rays OSLD had 6% higher sensitivity; the dose sensitivity was unchanged up to an accumulated dose of 20 Gy and thereafter decreased by 4% per 10 Gy of additional accumulated dose; dose sensitivity was not dependent on the angle of incidence of radiation; the OSLD in its light-tight case has an intrinsic buildup of 0.04 g/cm2; dose sensitivity of the OSLD was not dependent on temperature at the time of irradiation in the range of 10-40 degrees C. The clinical use of OSLDs for in vivo dosimetric measurements is shown to be feasible.

Characterization of optically stimulated luminescent dosimeters, OSLDs, for clinical dosimetric measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jursinic, Paul A.

2007-12-15

Optically stimulated luminescent dosimeters, OSLDs, are plastic disks infused with aluminum oxide doped with carbon (Al{sub 2}O{sub 3}:C). These disks are encased in a light-tight plastic holder. Crystals of Al{sub 2}O{sub 3}:C when exposed to ionizing radiation store energy that is released as luminescence (420 nm) when the OSLD is illuminated with stimulation light (540 nm). The intensity of the luminescence depends on the dose absorbed by the OSLD and the intensity of the stimulation light. OSLDs used in this work were InLight/OSL Dot dosimeters, which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). The following are dosimetricmore » properties of the OSLD that were determined: After a single irradiation, repeated readings cause the signal to decrease by 0.05% per reading; the signal could be discharged by greater than 98% by illuminating them for more than 45 s with a 150 W tungsten-halogen light; after irradiation there was a transient signal that decayed with a 0.8 min halftime; after the transient signal decay the signal was stable for days; repeated irradiations and readings of an individual OSLD gave a signal with a coefficient of variation of 0.6%; the dose sensitivity of OSLDs from a batch of detectors has a coefficient of variation of 0.9%, response was linear with absorbed dose over a test range of 1-300 cGy; above 300 cGy a small supra-linear behavior occurs; there was no dose-per-pulse dependence over a 388-fold range; there was no dependence on radiation energy or mode for 6 and 15 MV x rays and 6-20 MeV electrons; for Ir-192 gamma rays OSLD had 6% higher sensitivity; the dose sensitivity was unchanged up to an accumulated dose of 20 Gy and thereafter decreased by 4% per 10 Gy of additional accumulated dose; dose sensitivity was not dependent on the angle of incidence of radiation; the OSLD in its light-tight case has an intrinsic buildup of 0.04 g/cm{sup 2}; dose sensitivity of the OSLD was not dependent on temperature at the time of irradiation in the range of 10-40 deg. C. The clinical use of OSLDs for in vivo dosimetric measurements is shown to be feasible.« less

Dosimetric correlations of acute esophagitis in lung cancer patients treated with radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takeda, Ken; Nemoto, Kenji; Saito, Haruo

2005-07-01

Purpose: To evaluate the factors associated with acute esophagitis in lung cancer patients treated with thoracic radiotherapy. Methods and Materials: We examined 35 patients with non-small-cell lung cancer (n = 27, 77%) and small-cell lung cancer (n = 8, 23%) treated with thoracic radiotherapy between February 2003 and November 2004. The median patient age was 70 years (range, 50-83 years). The disease stage was Stage I in 2 patients (6%), Stage II in 1 (3%), Stage IIIa in 10 (28%), Stage IIIb in 9 (26%), and Stage IV in 9 (26%); 4 patients (11%) had recurrent disease after surgery. Amore » median dose of 60 Gy (range, 50-67 Gy) was given to the isocenter and delivered in single daily fractions of 1.8 or 2 Gy. With heterogeneity corrections, the median given dose to the isocenter was 60.3 Gy (range, 49.9-67.2 Gy). Of the 35 patients, 30 (86%) received concurrent chemotherapy consisting of a platinum agent, cisplatin or carboplatin, combined with paclitaxel in 18 patients (52%), irinotecan hydrochloride in 7 (20%), vincristine sulfate and etoposide in 2 (5%), vinorelbine ditartrate in 1 (3%), etoposide in 1 (3%), and docetaxel in 1 patient (3%). Three of these patients underwent induction therapy with cisplatin and irinotecan hydrochloride, administered before thoracic radiotherapy, and concurrent chemotherapy. Esophageal toxicity was graded according to the Radiation Therapy Oncology Group criteria. The following factors were analyzed with respect to their association with Grade 1 or worse esophagitis by univariate and multivariate analyses: age, gender, concurrent chemotherapy, chemotherapeutic agents, maximal esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving >10 to >65 Gy in 5-Gy increments. Results: Of the 35 patients, 25 (71%) developed acute esophagitis, with Grade 1 in 20 (57%) and Grade 2 in 5 (14%). None of the patients had Grade 3 or worse toxicity. The most significant correlation was between esophagitis and percentage of esophageal volume receiving >35 Gy on univariate (p = 0.002) and multivariate (p = 0.018) analyses. Conclusion: The percentage of esophageal volume receiving >35 Gy was the most statistically significant factor associated with mild acute esophagitis.« less

Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects.

PubMed

Shin, Dongseong; Lee, SeungHwan; Yi, Sojeong; Yoon, Seo Hyun; Cho, Joo-Youn; Bahng, Mi Young; Jang, In-Jin; Yu, Kyung-Sang

2017-01-01

DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects. A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated. After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2-3 h and was eliminated with terminal elimination half-life of 17.9-28.7 h. The mean renal clearance was 3.7-5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20-80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized C max and AUC 0- t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported. In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20-80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less.

Measurement of stray neutron doses inside the treatment room from a proton pencil beam scanning system.

PubMed

Mojżeszek, N; Farah, J; Kłodowska, M; Ploc, O; Stolarczyk, L; Waligórski, M P R; Olko, P

2017-02-01

To measure the environmental doses from stray neutrons in the vicinity of a solid slab phantom as a function of beam energy, field size and modulation width, using the proton pencil beam scanning (PBS) technique. Measurements were carried out using two extended range WENDI-II rem-counters and three tissue equivalent proportional counters. Detectors were suitably placed at different distances around the RW3 slab phantom. Beam irradiation parameters were varied to cover the clinical ranges of proton beam energies (100-220MeV), field sizes ((2×2)-(20×20)cm 2 ) and modulation widths (0-15cm). For pristine proton peak irradiations, large variations of neutron H ∗ (10)/D were observed with changes in beam energy and field size, while these were less dependent on modulation widths. H ∗ (10)/D for pristine proton pencil beams varied between 0.04μSvGy -1 at beam energy 100MeV and a (2×2)cm 2 field at 2.25m distance and 90° angle with respect to the beam axis, and 72.3μSvGy -1 at beam energy 200MeV and a (20×20) cm 2 field at 1m distance along the beam axis. The obtained results will be useful in benchmarking Monte Carlo calculations of proton radiotherapy in PBS mode and in estimating the exposure to stray radiation of the patient. Such estimates may be facilitated by the obtained best-fitted simple analytical formulae relating the stray neutron doses at points of interest with beam irradiation parameters. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Resumption of High-dose Methotrexate after Acute Kidney Injury and Glucarpidase Use in Pediatric Oncology Patients

PubMed Central

Christensen, Anthony M.; Pauley, Jennifer L.; Molinelli, Alejandro R.; Panetta, John C.; Ward, Deborah A.; Stewart, Clinton F.; Hoffman, James M.; Howard, Scott C.; Pui, Ching-Hon; Pappo, Alberto S.; Relling, Mary V.; Crews, Kristine R.

2013-01-01

Background High-dose methotrexate (HDMTX)-induced acute kidney injury is a rare but life-threatening complication. The methotrexate rescue agent glucarpidase rapidly hydrolyzes methotrexate to inactive metabolites. We retrospectively reviewed glucarpidase use in pediatric cancer patients at our institution and evaluated whether subsequent resumption of HDMTX was tolerated. Methods Clinical data and outcomes of all patients who received glucarpidase after HDMTX administration were reviewed. Results Of 1,141 patients treated with 4,909 courses of HDMTX, 20 patients (1.8% of patients, 0.4% of courses) received 22 doses of glucarpidase. The median glucarpidase dosage was 51.6 units/kg (range, 13 – 65.6 units/kg). At the time of administration, the median plasma methotrexate concentration was 29.1 µM (range, 1.3 – 590.6 µM). Thirteen of the 20 patients received a total of 39 courses of HDMTX therapy after glucarpidase. The median time to complete methotrexate excretion was 355 hours (range, 244 – 763 hours) for the HDMTX course during which glucarpidase was administered, 90 hours (range, 66 – 268 hours) for the next HDMTX course, and 72 hours (range, 42 – 116 hours) for subsequent courses. The median peak serum creatinine during these HDMTX courses was 2.2 mg/dL (range, 0.8 – 9.6 mg/dL), 0.8 mg/dL (range, 0.4 – 1.6 mg/dL), and 0.6 mg/dL (range, 0.4 – 0.9 mg/dL), respectively. One patient experienced nephrotoxicity upon rechallenge with HDMTX. Renal function eventually returned to baseline in all patients and no patient died as a result of methotrexate toxicity. Conclusion It is possible to safely resume HDMTX therapy after glucarpidase treatment for HDMTX-induced acute kidney injury. PMID:22252903

TH-A-19A-06: Site-Specific Comparison of Analytical and Monte Carlo Based Dose Calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuemann, J; Grassberger, C; Paganetti, H

2014-06-15

Purpose: To investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict dose distributions and to verify currently used uncertainty margins in proton therapy. Methods: Dose distributions predicted by an analytical pencilbeam algorithm were compared with Monte Carlo simulations (MCS) using TOPAS. 79 complete patient treatment plans were investigated for 7 disease sites (liver, prostate, breast, medulloblastoma spine and whole brain, lung and head and neck). A total of 508 individual passively scattered treatment fields were analyzed for field specific properties. Comparisons based on target coverage indices (EUD, D95, D90 and D50)more » were performed. Range differences were estimated for the distal position of the 90% dose level (R90) and the 50% dose level (R50). Two-dimensional distal dose surfaces were calculated and the root mean square differences (RMSD), average range difference (ARD) and average distal dose degradation (ADD), the distance between the distal position of the 80% and 20% dose levels (R80- R20), were analyzed. Results: We found target coverage indices calculated by TOPAS to generally be around 1–2% lower than predicted by the analytical algorithm. Differences in R90 predicted by TOPAS and the planning system can be larger than currently applied range margins in proton therapy for small regions distal to the target volume. We estimate new site-specific range margins (R90) for analytical dose calculations considering total range uncertainties and uncertainties from dose calculation alone based on the RMSD. Our results demonstrate that a reduction of currently used uncertainty margins is feasible for liver, prostate and whole brain fields even without introducing MC dose calculations. Conclusion: Analytical dose calculation algorithms predict dose distributions within clinical limits for more homogeneous patients sites (liver, prostate, whole brain). However, we recommend treatment plan verification using Monte Carlo simulations for patients with complex geometries.« less

Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer.

PubMed

Guckenberger, Matthias; Klement, Rainer Johannes; Allgäuer, Michael; Appold, Steffen; Dieckmann, Karin; Ernst, Iris; Ganswindt, Ute; Holy, Richard; Nestle, Ursula; Nevinny-Stickel, Meinhard; Semrau, Sabine; Sterzing, Florian; Wittig, Andrea; Andratschke, Nicolaus; Flentje, Michael

2013-10-01

To compare the linear-quadratic (LQ) and the LQ-L formalism (linear cell survival curve beyond a threshold dose dT) for modeling local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC). This study is based on 395 patients from 13 German and Austrian centers treated with SBRT for stage I NSCLC. The median number of SBRT fractions was 3 (range 1-8) and median single fraction dose was 12.5 Gy (2.9-33 Gy); dose was prescribed to the median 65% PTV encompassing isodose (60-100%). Assuming an α/β-value of 10 Gy, we modeled TCP as a sigmoid-shaped function of the biologically effective dose (BED). Models were compared using maximum likelihood ratio tests as well as Bayes factors (BFs). There was strong evidence for a dose-response relationship in the total patient cohort (BFs>20), which was lacking in single-fraction SBRT (BFs<3). Using the PTV encompassing dose or maximum (isocentric) dose, our data indicated a LQ-L transition dose (dT) at 11 Gy (68% CI 8-14 Gy) or 22 Gy (14-42 Gy), respectively. However, the fit of the LQ-L models was not significantly better than a fit without the dT parameter (p=0.07, BF=2.1 and p=0.86, BF=0.8, respectively). Generally, isocentric doses resulted in much better dose-response relationships than PTV encompassing doses (BFs>20). Our data suggest accurate modeling of local tumor control in fractionated SBRT for stage I NSCLC with the traditional LQ formalism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Analysis and optimization of coagulation and flocculation process

NASA Astrophysics Data System (ADS)

Saritha, V.; Srinivas, N.; Srikanth Vuppala, N. V.

2017-03-01

Natural coagulants have been the focus of research of many investigators through the last decade owing to the problems caused by the chemical coagulants. Optimization of process parameters is vital for the effectiveness of coagulation process. In the present study optimization of parameters like pH, dose of coagulant and mixing speed were studied using natural coagulants sago and chitin in comparison with alum. Jar test apparatus was used to perform the coagulation. The results showed that the removal of turbidity was up to 99 % by both alum and chitin at lower doses of coagulant, i.e., 0.1-0.3 g/L, whereas sago has shown a reduction of 70-100 % at doses of 0.1 and 0.2 g/L. The optimum conditions observed for sago were 6 and 7 whereas chitin was stable at all pH ranges, lower coagulant doses, i.e., 0.1-0.3 g/L and mixing speed—rapid mixing at 100 rpm for 10 min and slow mixing 20 rpm for 20 min. Hence, it can be concluded that sago and chitin can be used for treating water even with large seasonal variation in turbidity.

Radiation exposure assessment for portsmouth naval shipyard health studies.

PubMed

Daniels, R D; Taulbee, T D; Chen, P

2004-01-01

Occupational radiation exposures of 13,475 civilian nuclear shipyard workers were investigated as part of a retrospective mortality study. Estimates of annual, cumulative and collective doses were tabulated for future dose-response analysis. Record sets were assembled and amended through range checks, examination of distributions and inspection. Methods were developed to adjust for administrative overestimates and dose from previous employment. Uncertainties from doses below the recording threshold were estimated. Low-dose protracted radiation exposures from submarine overhaul and repair predominated. Cumulative doses are best approximated by a hybrid log-normal distribution with arithmetic mean and median values of 20.59 and 3.24 mSv, respectively. The distribution is highly skewed with more than half the workers having cumulative doses <10 mSv and >95% having doses <100 mSv. The maximum cumulative dose is estimated at 649.39 mSv from 15 person-years of exposure. The collective dose was 277.42 person-Sv with 96.8% attributed to employment at Portsmouth Naval Shipyard.

The relationship of human milk leptin and macronutrients with gastric emptying in term breastfed infants.

PubMed

Cannon, Anna M; Gridneva, Zoya; Hepworth, Anna R; Lai, Ching T; Tie, Wan J; Khan, Sadaf; Hartmann, Peter E; Geddes, Donna T

2017-07-01

BackgroundInfants breastfed on demand exhibit a variety of feeding patterns and self-regulate their nutrient intake, but factors influencing their gastric emptying (GE) are poorly understood. Despite research into appetite regulation properties of leptin, there is limited information about relationships between human milk leptin and infant GE.MethodsGastric volumes were calculated from ultrasound scans of infants' stomachs (n=20) taken before and after breastfeeding, and then every 12.5 min (median; range: 3-45 min) until the next feed. Skim milk leptin and macronutrient concentrations were measured and doses were calculated.ResultsThe leptin concentration was (mean±SD) 0.51±0.16 ng/ml; the leptin dose was 45.5±20.5 ng per feed. No relationships between both concentration and dose of leptin and time between the feeds (P=0.57; P=1, respectively) or residual stomach volumes before the subsequent feed (P=0.20; P=0.050) were found. Post-feed stomach volumes (GE rate) were not associated with leptin concentration (P=0.77) or dose (P=0.85).ConclusionGE in term breastfed infants was not associated with either skim milk leptin concentration or dose. Further investigation with inclusion of whole-milk leptin and other hormones that affect gastrointestinal activity is warranted.

Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations

PubMed Central

de Abajo, Francisco J; García Rodríguez, Luis A

2001-01-01

Background The use of low-dose aspirin has been reported to be associated with an increased risk of upper gastrointestinal complications (UGIC). The coating of aspirin has been proposed as an approach to reduce such a risk. To test this hypothesis, we carried out a population based case-control study. Methods We identified incident cases of UGIC (bleeding or perforation) aged 40 to 79 years between April 1993 to October 1998 registered in the General Practice Research Database. Controls were selected randomly from the source population. Adjusted estimates of relative risk (RR) associated with current use of aspirin as compared to non use were computed using unconditional logistic regression. Results We identified 2,105 cases of UGIC and selected 11,500 controls. Among them, 287 (13.6%) cases and 837 (7.3%) controls were exposed to aspirin, resulting in an adjusted RR of 2.0 (1.7-2.3). No clear dose-effect was found within the range of 75-300 mg. The RR associated with enteric-coated formulations (2.3, 1.6-3.2) was similar to the one of plain aspirin (1.9, 1.6-2.3), and no difference was observed depending on the site. The first two months of treatment was the period of greater risk (RR= 4.5, 2.9-7.1). The concomitant use of aspirin with high-dose NSAIDs greatly increased the risk of UGIC (13.3, 8.5-20.9) while no interaction was apparent with low-medium doses (2.2, 1.0-4.6). Conclusions Low-dose aspirin increases by twofold the risk of UGIC in the general population and its coating does not modify the effect. Concomitant use of low-dose aspirin and NSAIDs at high doses put patients at a specially high risk of UGIC. PMID:11228592

SU-F-T-307: Peripheral Dose Comparison Between Static and Dynamic Jaw Tracking On a High Definition MLC System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez-Andujar, A; Cheung, J; Chuang, C

Purpose: To investigate the effect of dynamic and static jaw tracking on patient peripheral doses. Materials and Methods: A patient plan with a large sacral metastasis (volume 800cm3, prescription 600cGyx5) was selected for this study. The plan was created using 2-field RapidArc with jaw tracking enabled (Eclipse, V11.0.31). These fields were then exported and edited in MATLAB with static jaw positions using the control point with the largest field size for each respective arc, but preserving the optimized leaf sequences for delivery. These fields were imported back into Eclipse for dose calculation and comparison and copied to a Rando phantommore » for delivery analysis. Points were chosen in the phantom at depth and on the phantom surface at locations outside the primary radiation field, at distances of 12cm, 20cm, and 30cm from the isocenter. Measurements were acquired with OSLDs placed at these positions in the phantom with both the dynamic and static jaw deliveries for comparison. Surface measurements included an additional 1cm bolus over the OSLDs to ensure electron equilibrium. Results: The static jaw deliveries resulted in cumulative jaw-defined field sizes of 17.3% and 17.4% greater area than the dynamic jaw deliveries for each arc. The static jaw plan resulted in very small differences in calculated dose in the treatment planning system ranging from 0–16cGy. The measured dose differences were larger than calculated, but the differences in absolute dose were small. The measured dose differences at depth (surface) between the two deliveries showed an increase for the static jaw delivery of 2.2%(11.4%), 15.6%(20.0%), and 12.7%(12.7%) for distances of 12cm, 20cm, and 30cm, respectively. Eclipse calculates a difference of 0–3.1% for all of these points. The largest absolute dose difference between all points was 6.2cGy. Conclusion: While we demonstrated larger than expected differences in peripheral dose, the absolute dose differences were small.« less

SU-E-T-629: Feasibility Study of Treating Multiple Brain Tumors with Large Number of Noncoplanar IMRT Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, P; Ma, L

Purpose: To study the feasibility of treating multiple brain tumors withlarge number of noncoplanar IMRT beams. Methods: Thirty beams are selected from 390 deliverable beams separated by six degree in 4pi space. Beam selection optimization is based on a column generation algorithm. MLC leaf size is 2 mm. Dose matrices are calculated with collapsed cone convolution and superposition method in a 2 mm by 2mm by 2 mm grid. Twelve brain tumors of various shapes, sizes and locations are used to generate four plans treating 3, 6, 9 and 12 tumors. The radiation dose was 20 Gy prescribed to themore » 100% isodose line. Dose Volume Histograms for tumor and brain were compared. Results: All results are based on a 2 mm by 2 mm by 2 mm CT grid. For 3, 6, 9 and 12 tumor plans, minimum tumor doses are all 20 Gy. Mean tumor dose are 20.0, 20.1, 20.1 and 20.1 Gy. Maximum tumor dose are 23.3, 23.6, 25.4 and 25.4 Gy. Mean ventricles dose are 0.7, 1.7, 2.4 and 3.1 Gy.Mean subventricular zone dose are 0.8, 1.3, 2.2 and 3.2 Gy. Average Equivalent uniform dose (gEUD) values for tumor are 20.1, 20.1, 20.2 and 20.2 Gy. The conformity index (CI) values are close to 1 for all 4 plans. The gradient index (GI) values are 2.50, 2.05, 2.09 and 2.19. Conclusion: Compared with published Gamma Knife treatment studies, noncoplanar IMRT treatment plan is superior in terms of dose conformity. Due to maximum limit of beams per plan, Gamma knife has to treat multiple tumors separately in different plans. Noncoplanar IMRT plans theoretically can be delivered in a single plan on any modern linac with an automated couch and image guidance. This warrants further study of using noncoplanar IMRT as a viable treatment solution for multiple brain tumors.« less

Intravenous Lidocaine as an Adjuvant for Pain Associated with Sickle Cell Disease.

PubMed

Nguyen, Natalie L; Kome, Anne M; Lowe, Denise K; Coyne, Patrick; Hawks, Kelly G

2015-01-01

The objectives of this study were to evaluate the efficacy and safety of adjuvant intravenous (IV) lidocaine in adults with sickle cell disease (SCD). This was a retrospective review. Adults with SCD receiving at least one IV lidocaine infusion from 2004 to 2014 were included. Patient demographics, lidocaine treatment parameters, pain scores, pain medications, and adverse effects were recorded. Eleven patients were identified, yielding 15 IV lidocaine trials. Clinical improvement in pain scores from pre-lidocaine challenge to 24 hours post-lidocaine challenge, defined by ≥ 20% reduction in pain scores, was achieved in 53.3% (8 of 15) of IV lidocaine challenges. Of the 8 clinically successful trials, the mean reduction in morphine dose equivalents (MDE) from 24 hours pre-lidocaine challenge to 24 hours post-lidocaine challenge was 32.2%. Additionally, clinically successful trials had a mean initial and a maximum dose of 1 mg/kg/h (range: 0.5-2.7 mg/kg/h) and 1.3 mg/kg/h (range: 0.5-1.9 mg/kg/h), respectively. On average, these patients underwent 3 dose titrations (range: 1-8) and received lidocaine infusions for 4.4 days (range: 2-8 days). Two patients experienced disorientation and dizziness. The authors conclude that adjuvant IV lidocaine provided pain relief and a mean reduction in MDE during sickle cell pain crisis. These results provide preliminary insight into the use of IV lidocaine for treating pain in patients with SCD, although prospective studies are needed to determine efficacy, dosing, and tolerability of IV lidocaine in this patient population.

Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial.

PubMed

Mayer, Kenneth H; Seaton, Kelly E; Huang, Yunda; Grunenberg, Nicole; Isaacs, Abby; Allen, Mary; Ledgerwood, Julie E; Frank, Ian; Sobieszczyk, Magdalena E; Baden, Lindsey R; Rodriguez, Benigno; Van Tieu, Hong; Tomaras, Georgia D; Deal, Aaron; Goodman, Derrick; Bailer, Robert T; Ferrari, Guido; Jensen, Ryan; Hural, John; Graham, Barney S; Mascola, John R; Corey, Lawrence; Montefiori, David C

2017-11-01

VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens. Additionally, this study aimed to assess the effect that the human body has on the functional activities of VRC01 as measured by several in vitro assays. Eighty-eight healthy, HIV-uninfected, low-risk participants were enrolled in 6 United States clinical research sites affiliated with the HVTN between September 9, 2014, and July 15, 2015. The median age of enrollees was 27 years (range, 18-50); 52% were White (non-Hispanic), 25% identified as Black (non-Hispanic), 11% were Hispanic, and 11% were non-Hispanic people of diverse origins. Participants were randomized to receive the following: a 40 mg/kg IV VRC01 loading dose followed by five 20 mg/kg IV VRC01 doses every 4 weeks (treatment group 1 [T1], n = 20); eleven 5 mg/kg subcutaneous (SC) VRC01 (treatment group 3 [T3], n = 20); placebo (placebo group 3 [P3], n = 4) doses every 2 weeks; or three 40 mg/kg IV VRC01 doses every 8 weeks (treatment group 2 [T2], n = 20). Treatment groups T4 and T5 (n = 12 each) received three 10 or 30 mg/kg IV VRC01 doses every 8 weeks, respectively. Participants were followed for 32 weeks after their first VRC01 administration and received a total of 249 IV infusions and 208 SC injections, with no serious adverse events, dose-limiting toxicities, nor evidence for anti-VRC01 antibodies observed. Serum VRC01 levels were detected through 12 weeks after final administration in all participants who received all scheduled doses. Mean peak serum VRC01 levels of 1,177 μg/ml (95% CI: 1,033, 1,340) and 420 μg/ml (95% CI: 356, 494) were achieved 1 hour after the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively. Mean trough levels at week 24 in the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively, were 16 μg/ml (95% CI: 10, 27) and 6 μg/ml (95% CI: 5, 9) levels, which neutralize a majority of circulating strains in vitro (50% inhibitory concentration [IC50] > 5 μg/ml). Post-infusion/injection serum VRC01 retained expected functional activity (virus neutralization, antibody-dependent cellular cytotoxicity, phagocytosis, and virion capture). The limitations of this study include the relatively small sample size of each VRC01 administration regimen and missing data from participants who were unable to complete all study visits. VRC01 administered as either an IV infusion (10-40 mg/kg) given monthly or bimonthly, or as an SC injection (5 mg/kg) every 2 weeks, was found to be safe and well tolerated. In addition to maintaining drug concentrations consistent with neutralization of the majority of tested HIV strains, VRC01 concentrations from participants' sera were found to avidly capture HIV virions and to mediate antibody-dependent cellular phagocytosis, suggesting a range of anti-HIV immunological activities, warranting further clinical trials. Clinical Trials Registration: NCT02165267.

Use of a control film piece in radiochromic film dosimetry.

PubMed

Aldelaijan, Saad; Alzorkany, Faisal; Moftah, Belal; Buzurovic, Ivan; Seuntjens, Jan; Tomic, Nada; Devic, Slobodan

2016-01-01

Radiochromic films change their color upon irradiation due to polymerization of the sensitive component embedded within the sensitive layer. However, agents, other than monitored radiation, can lead to a change in the color of the sensitive layer (temperature, humidity, UV light) that can be considered as a background signal and can be removed from the actual measurement by using a control film piece. In this work, we investigate the impact of the use of control film pieces on both accuracy and uncertainty of dose measured using radiochromic film based reference dosimetry protocol. We irradiated "control" film pieces (EBT3 GafChromic(TM) film model) to known doses in a range of 0.05-1 Gy, and five film pieces of the same size to 2, 5, 10, 15 and 20 Gy, considered to be "unknown" doses. Depending on a dose range, two approaches to incorporating control film piece were investigated: signal and dose corrected method. For dose values greater than 10 Gy, the increase in accuracy of 3% led to uncertainty loss of 5% by using dose corrected approach. At lower doses and signals of the order of 5%, we observed an increase in accuracy of 10% with a loss of uncertainty lower than 1% by using the corrected signal approach. Incorporation of the signal registered by the control film piece into dose measurement analysis should be a judgment call of the user based on a tradeoff between deemed accuracy and acceptable uncertainty for a given dose measurement. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Neutron dosimetry in low-earth orbit using passive detectors

NASA Technical Reports Server (NTRS)

Benton, E. R.; Benton, E. V.; Frank, A. L.

2001-01-01

This paper summarizes neutron dosimetry measurements made by the USF Physics Research Laboratory aboard US and Russian LEO spacecraft over the past 20 years using two types of passive detector. Thermal/resonance neutron detectors exploiting the 6Li(n,T) alpha reaction were used to measure neutrons of energies <1 MeV. Fission foil neutron detectors were used to measure neutrons of energies above 1 MeV. While originally analysed in terms of dose equivalent using the NCRP-38 definition of quality factor, for the purposes of this paper the measured neutron data have been reanalyzed and are presented in terms of ambient dose equivalent. Dose equivalent rate for neutrons <1 MeV ranged from 0.80 microSv/d on the low altitude, low inclination STS-41B mission to 22.0 microSv/d measured in the Shuttle's cargo bay on the highly inclined STS-51F Spacelab-2 mission. In one particular instance a detector embedded within a large hydrogenous mass on STS-61 (in the ECT experiment) measured 34.6 microSv/d. Dose equivalent rate measurements of neutrons >1 MeV ranged from 4.5 microSv/d on the low altitude STS-3 mission to 172 microSv/d on the 6 year LDEF mission. Thermal neutrons (<0.3 eV) were observed to make a negligible contribution to neutron dose equivalent in all cases. The major fraction of neutron dose equivalent was found to be from neutrons >1 MeV and, on LDEF, neutrons >1 MeV are responsible for over 98% of the total neutron dose equivalent. Estimates of the neutron contribution to the total dose equivalent are somewhat lower than model estimates, ranging from 5.7% at a location under low shielding on LDEF to 18.4% on the highly inclined (82.3 degrees) Biocosmos-2044 mission. c2001 Elsevier Science Ltd. All rights reserved.

[Pharmacokinetics and clinical studies of flomoxef in the pediatric field].

PubMed

Motohiro, T; Oda, K; Aramaki, M; Kawakami, A; Tanaka, K; Koga, T; Shimada, Y; Tomita, S; Sakata, Y; Fujimoto, T

1987-08-01

Flomoxef (FMOX, 6315-S), a new intravenous cephem antibiotics, was administered to a total of 11 cases with their ages ranging from 7 years and 4 months to 10 years and 10 months. Among them, two were administered with (FMOX at) a dose level of 10 mg/kg, three each with 20 mg/kg and 40 mg/kg using one shot intravenous injection, and the remaining 3 with 40 mg/kg by intravenous drip infusion over 30 minutes. Plasma concentrations, urine concentrations and urinary recovery rates were determined. The clinical efficacy of FMOX was evaluated in 2 cases with tonsillitis, 45 with acute pneumonia, 10 with urinary tract infections, 2 with purulent lymphadenitis, and 2 with abscess, a total of 61 cases. Of these cases, one case of pneumonia in which a side effect occurred was excluded from the evaluation because the treatment was interrupted short of the required period. In the remaining 60 cases, the mean daily dose was 79.3 mg/kg in 3 or 4 divided doses and, except one case treated by 30-minute intravenous drip infusion, all cases were treated by one shot intravenous injection for a mean period of 6 days. Bacteriological effects of FMOX, its side effects and influences on laboratory test values were also investigated. 1. Maximum plasma concentrations after one shot intravenous injections of FMOX occurred at 5 minutes after administration regardless of dose levels (10 mg/kg in 2 cases, 20 mg/kg in 3 and 40 mg/kg in 3). Mean peak values obtained upon the 3 different dose levels were 62.5, 103.1 and 244.7 micrograms/ml, respectively. Mean plasma half-lives were 0.670, 0.915 and 0.595 hour, and mean AUCs were 33.0, 65.2 and 133.1 micrograms.hr/ml, respectively. Thus, a positive dose-response relationship was found among the 3 doses. 2. Plasma concentrations after 30-minute intravenous drip infusions of FMOX at 40 mg/kg always reached a peak at 30 minutes after the initiation of infusion, i.e. at the completion of infusion, and the mean value for 3 administrations was 151.0 micrograms/ml. The mean half-life was 0.973 hour and the mean AUC was 149.1 micrograms.hr/ml. 3. Maximum concentrations in urine after one shot intravenous injections of FMOX were always obtained in 0 approximately 2 hours after administration regardless of dose levels (10 mg/kg, 2 cases, 20 mg/kg, 3 cases and at 40 mg/kg, 3 cases) and mean values for the 3 dose levels were 2,570, 4,410 and 6,290 micrograms/ml, respectively. Thus, urine concentrations were also dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volotskova, O; Xu, A; Jozsef, G

Purpose: To investigate the response and dose rate dependence of a scintillation detector over a wide energy range. Methods: The energy dependence of W1 scintillation detector was tested with: 1) 50–225 keV beams generated by an animal irradiator, 2) a Leksell Gamma Knife Perfexion Co-60 source, 3) 6MV, 6FFF, 10FFF and 15MV photon beams, and 4) 6–20MeV electron beams from a linac. Calibrated linac beams were used to deliver 100 cGy to the detector at dmax in water under reference conditions. The gamma-knife measurement was performed in solid water (100 cGy with 16mm collimator). The low energy beams were calibratedmore » with an ion chamber in air (TG-61), and the scintillation detector was placed at the same location as the ionization chamber during calibration. For the linac photon and electron beams, dose rate dependence was tested for 100–2400 and 100–800 MU/min. Results: The scintillation detector demonstrated strong energy dependence in the range of 50–225keV. The measured values were lower than the delivered dose and increased as the energy increased. Therapeutic photon beams showed energy independence with variations less than 1%. Therapeutic electron beams displayed the same sensitivity of ∼2–3% at their corresponding dmax depths. The change in dose-rate of photon and electron beams within the therapeutic energy range did not affect detector output (<0.5%). Measurements acquired with the gamma knife showed that the output data agreed with the delivered dose up to 3%. Conclusion: W1 scintillation detector output has a strong energy dependence in the diagnostic and orthovoltage energy range. Therapeutic photon beams exhibited energy independence with no observable dose-rate dependence. This study may aid in the implementation of a scintillation detector in QA programs by providing energy calibration factors.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kieselmann, J; Bartzsch, S; Oelfke, U

Purpose: Microbeam Radiation Therapy is a preclinical method in radiation oncology that modulates radiation fields on a micrometre scale. Dose calculation is challenging due to arising dose gradients and therapeutically important dose ranges. Monte Carlo (MC) simulations, often used as gold standard, are computationally expensive and hence too slow for the optimisation of treatment parameters in future clinical applications. On the other hand, conventional kernel based dose calculation leads to inaccurate results close to material interfaces. The purpose of this work is to overcome these inaccuracies while keeping computation times low. Methods: A point kernel superposition algorithm is modified tomore » account for tissue inhomogeneities. Instead of conventional ray tracing approaches, methods from differential geometry are applied and the space around the primary photon interaction is locally warped. The performance of this approach is compared to MC simulations and a simple convolution algorithm (CA) for two different phantoms and photon spectra. Results: While peak doses of all dose calculation methods agreed within less than 4% deviations, the proposed approach surpassed a simple convolution algorithm in accuracy by a factor of up to 3 in the scatter dose. In a treatment geometry similar to possible future clinical situations differences between Monte Carlo and the differential geometry algorithm were less than 3%. At the same time the calculation time did not exceed 15 minutes. Conclusion: With the developed method it was possible to improve the dose calculation based on the CA method with respect to accuracy especially at sharp tissue boundaries. While the calculation is more extensive than for the CA method and depends on field size, the typical calculation time for a 20×20 mm{sup 2} field on a 3.4 GHz and 8 GByte RAM processor remained below 15 minutes. Parallelisation and optimisation of the algorithm could lead to further significant calculation time reductions.« less

WE-AB-207B-12: Prospective Study of the Relationship Between Dose-Volume Clinical Toxicity and Patient Reported Outcomes in Lung Cancer Patients Treated with SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayyas, E; Vance, S; Brown, S

Purpose: To determine in a prospective study, the correlation between radiation dose/volume, clinical toxicities and patient-reported, quality of life (QOL) resulting from lung SBRT. Methods: For 106 non-small cell lung cancer (NSCLC) patients receiving SBRT (12 Gy × 4), symptoms including cough, dyspnea, fatigue and pneumonitis were measured at baseline (before treatment), after treatment and 3, 6, and 12 months post-treatment. Toxicity was graded from zero to five. Dosimetric parameters such as the MLD, D10%, D20%, and lung subvolumes (V10 and V20) were obtained from the treatment plan. Dosimetric parameters and number of patients demonstrating toxicity ≥ grade 2 weremore » tabulated. Linear regression analysis was used to calculate correlations between MLD and D10, D20, V10 and V20. Results: The percentages of patients with > grade 2 pneumonitis, fatigue, cough, and dyspnea over 3 to 12 months increased from 0.0% to 3.5%, 3.2% to 10.5%, 4.3% to 8.3%, and 10.8% to 18.8%, respectively. Computed dose indices D10%, D20% were 7.9±4.8 Gy and 3.0±2.3 Gy, respectively. MLD ranged from 0.34 Gy up to 9.9 Gy with overall average 3.0±1.7 Gy. The averages of the subvolumes V10 and V20 were respectively 8.9±5.3% and 3.0±2.4%. The linear regression analysis showed that V10 and D10 demonstrated the strongest correlation to MLD; R2= 0.92 and 0.87, respectively. V20, and D20 were also strongly correlated with MLD; R2 = 0.81 and 0.84 respectively. A correlation was also found to exist between MLD > 2 Gy and ≥ grade 2 cough and dyspnea. Subvolume values for 2Gy MLD were 5.3% for V10 and 2% for V20. Conclusion: Dosimetric indices: MLD ≥ 2Gy, D10 ≥ 5Gy and V10 ≥ 5% of the total lung volume were predictive of > grade 2 cough and dyspnea QOL data. The QOL results are a novel component of this work. acknowledgement of the Varian grant support.« less

Single dose x irradiation and concomitant hyperthermia on a murine fibroscarcoma. [Sensitizing effects of hyperthermia on tumors in mice subjected to local radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn, E.W.; Alfieri, A.A.; Kim, J.H.

1978-12-01

The objectives of this study were to quantitate the effects of local tumor hyperthermia (LTH) and concomitant x irradiation (RAD) on a moderately radioresistant murine fibrosarcoma in situ. Comparisons were made to the combined treatment response on the Ridgway osteogenic sarcoma, a radiosensitive tumor previously used in this laboratory and to establish the Meth-A fibrosarcoma as a model system for combined modality studies. 1.0 cm/sup 3/ tumors were exposed to single doses of RAD ranging from 0.5 to 3.8 krad alone or 0.5 to 2.3 krad in combination with LTH (water bath at 43.1 +- .05 C for 20 minutes)more » applied immediately postirradiation. LTH significantly enhanced the action of radiation as measured by tumor volume analysis, mean survival time and cures. The ratio of radiation doses vs. RAD + LTH required to produce an equivalent response ranged from 1.4 to 2.5 depending upon the endpoints evaluated. These findings are consistent with single dose studies on the radiosensitive Ridgway osteogenic sarcoma and suggest that the tumoricidal effectiveness of combination radiation and hyperthermia cannot be predicted on the basis of the radiation alone responsiveness of tumor.« less

Late Infection-Related Mortality in Asplenic Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

PubMed

Weil, Brent R; Madenci, Arin L; Liu, Qi; Howell, Rebecca M; Gibson, Todd M; Yasui, Yutaka; Neglia, Joseph P; Leisenring, Wendy M; Smith, Susan A; Tonorezos, Emily S; Friedman, Danielle N; Constine, Louis S; Tinkle, Christopher L; Diller, Lisa R; Armstrong, Gregory T; Oeffinger, Kevin C; Weldon, Christopher B

2018-06-01

Purpose Infection-related outcomes associated with asplenia or impaired splenic function in survivors of childhood cancer remains understudied. Methods Late infection-related mortality was evaluated in 20,026 5-year survivors of childhood cancer (diagnosed < 21 years of age from 1970 to 1999; median age at diagnosis, 7.0 years [range, 0 to 20 years]; median follow-up, 26 years [range, 5 to 44 years]) using cumulative incidence and piecewise-exponential regression models to estimate adjusted relative rates (RRs). Splenic radiation was approximated using average dose (direct and/or indirect) to the left upper quadrant of the abdomen (hereafter, referred to as splenic radiation). Results Within 5 years of diagnosis, 1,354 survivors (6.8%) had a splenectomy and 9,442 (46%) had splenic radiation without splenectomy. With 62 deaths, the cumulative incidence of infection-related late mortality was 1.5% (95% CI, 0.7% to 2.2%) at 35 years after splenectomy and 0.6% (95% CI, 0.4% to 0.8%) after splenic radiation. Splenectomy (RR, 7.7; 95% CI, 3.1 to 19.1) was independently associated with late infection-related mortality. Splenic radiation was associated with increasing risk for late infection-related mortality in a dose-response relationship (0.1 to 9.9 Gy: RR, 2.0; 95% CI, 0.9 to 4.5; 10 to 19.9 Gy: RR, 5.5; 95% CI, 1.9 to 15.4; ≥ 20 Gy: RR, 6.0; 95% CI, 1.8 to 20.2). High-dose alkylator chemotherapy exposure was also independently associated with an increased risk of infection-related mortality (RR, 1.9; 95% CI, 1.1 to 3.4). Conclusion Splenectomy and splenic radiation significantly increase risk for late infection-related mortality. Even low- to intermediate-dose radiation exposure confers increased risk, suggesting that the spleen is highly radiosensitive. These findings should inform long-term follow-up guidelines for survivors of childhood cancer and should lead clinicians to avoid or reduce radiation exposure involving the spleen whenever possible.

A phase 2a randomized, parallel group, dose-ranging study of molindone in children with attention-deficit/hyperactivity disorder and persistent, serious conduct problems.

PubMed

Stocks, Jennifer Dugan; Taneja, Baldeo K; Baroldi, Paolo; Findling, Robert L

2012-04-01

To evaluate safety and tolerability of four doses of immediate-release molindone hydrochloride in children with attention-deficit/hyperactivity disorder (ADHD) and serious conduct problems. This open-label, parallel-group, dose-ranging, multicenter trial randomized children, aged 6-12 years, with ADHD and persistent, serious conduct problems to receive oral molindone thrice daily for 9-12 weeks in four treatment groups: Group 1-10 mg (5 mg if weight <30 kg), group 2-20 mg (10 mg if <30 kg), group 3-30 mg (15 mg if <30 kg), and group 4-40 mg (20 mg if <30 kg). The primary outcome measure was to evaluate safety and tolerability of molindone in children with ADHD and serious conduct problems. Secondary outcome measures included change in Nisonger Child Behavior Rating Form-Typical Intelligence Quotient (NCBRF-TIQ) Conduct Problem subscale scores, change in Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I) subscale scores from baseline to end point, and Swanson, Nolan, and Pelham rating scale-revised (SNAP-IV) ADHD-related subscale scores. The study randomized 78 children; 55 completed the study. Treatment with molindone was generally well tolerated, with no clinically meaningful changes in laboratory or physical examination findings. The most common treatment-related adverse events (AEs) included somnolence (n=9), weight increase (n=8), akathisia (n=4), sedation (n=4), and abdominal pain (n=4). Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). The incidence of AEs and treatment-related AEs increased with increasing dose. NCBRF-TIQ subscale scores improved in all four treatment groups, with 34%, 34%, 32%, and 55% decreases from baseline in groups 1, 2, 3, and 4, respectively. CGI-S and SNAP-IV scores improved over time in all treatment groups, and CGI-I scores improved to the greatest degree in group 4. Molindone at doses of 5-20 mg/day (children weighing <30 kg) and 20-40 mg (≥ 30 kg) was well tolerated, and preliminary efficacy results suggest that molindone produces dose-related behavioral improvements over 9-12 weeks. Additional double-blind, placebo-controlled trials are needed to further investigate molindone in this pediatric population.

Effect of γ-dose rate and total dose interrelation on the polymeric hydrogel: A novel injectable male contraceptive

NASA Astrophysics Data System (ADS)

Jha, Pradeep K.; Jha, Rakhi; Gupta, B. L.; Guha, Sujoy K.

2010-05-01

Functional necessity to use a particular range of dose rate and total dose of γ-initiated polymerization to manufacture a novel polymeric hydrogel RISUG ® (reversible inhibition of sperm under guidance) made of styrene maleic anhydride (SMA) dissolved in dimethyl sulphoxide (DMSO), for its broad biomedical application explores new dimension of research. The present work involves 16 irradiated samples. They were tested by fourier transform infrared spectroscopy, matrix assisted laser desorption/ionization-TOF, field emission scanning electron microscopy, high resolution transmission electron microscopy, etc. to see the interrelation effect of gamma dose rates (8.25, 17.29, 20.01 and 25.00 Gy/min) and four sets of doses (1.8, 2.0, 2.2 and 2.4 kGy) on the molecular weight, molecular weight distribution and porosity analysis of the biopolymeric drug RISUG ®. The results of randomized experiment indicated that a range of 18-24 Gy/min γ-dose rate and 2.0-2.4 kGy γ-total doses is suitable for the desirable in vivo performance of the contraceptive copolymer.

SU-F-T-74: Experimental Validation of Monaco Electron Monte Carlo Dose Calculation for Small Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varadhan; Way, S; Arentsen, L

2016-06-15

Purpose: To verify experimentally the accuracy of Monaco (Elekta) electron Monte Carlo (eMC) algorithm to calculate small field size depth doses, monitor units and isodose distributions. Methods: Beam modeling of eMC algorithm was performed for electron energies of 6, 9, 12 15 and 18 Mev for a Elekta Infinity Linac and all available ( 6, 10, 14 20 and 25 cone) applicator sizes. Electron cutouts of incrementally smaller field sizes (20, 40, 60 and 80% blocked from open cone) were fabricated. Dose calculation was performed using a grid size smaller than one-tenth of the R{sub 80–20} electron distal falloff distancemore » and number of particle histories was set at 500,000 per cm{sup 2}. Percent depth dose scans and beam profiles at dmax, d{sub 90} and d{sub 80} depths were measured for each cutout and energy with Wellhoffer (IBA) Blue Phantom{sup 2} scanning system and compared against eMC calculated doses. Results: The measured dose and output factors of incrementally reduced cutout sizes (to 3cm diameter) agreed with eMC calculated doses within ± 2.5%. The profile comparisons at dmax, d{sub 90} and d{sub 80} depths and percent depth doses at reduced field sizes agreed within 2.5% or 2mm. Conclusion: Our results indicate that the Monaco eMC algorithm can accurately predict depth doses, isodose distributions, and monitor units in homogeneous water phantom for field sizes as small as 3.0 cm diameter for energies in the 6 to 18 MeV range at 100 cm SSD. Consequently, the old rule of thumb to approximate limiting cutout size for an electron field determined by the lateral scatter equilibrium (E (MeV)/2.5 in centimeters of water) does not apply to Monaco eMC algorithm.« less

Golden Rice is an effective source of vitamin A.

PubMed

Tang, Guangwen; Qin, Jian; Dolnikowski, Gregory G; Russell, Robert M; Grusak, Michael A

2009-06-01

Genetically engineered "Golden Rice" contains up to 35 microg beta-carotene per gram of rice. It is important to determine the vitamin A equivalency of Golden Rice beta-carotene to project the potential effect of this biofortified grain in rice-consuming populations that commonly exhibit low vitamin A status. The objective was to determine the vitamin A value of intrinsically labeled dietary Golden Rice in humans. Golden Rice plants were grown hydroponically with heavy water (deuterium oxide) to generate deuterium-labeled [2H]beta-carotene in the rice grains. Golden Rice servings of 65-98 g (130-200 g cooked rice) containing 0.99-1.53 mg beta-carotene were fed to 5 healthy adult volunteers (3 women and 2 men) with 10 g butter. A reference dose of [13C10]retinyl acetate (0.4-1.0 mg) in oil was given to each volunteer 1 wk before ingestion of the Golden Rice dose. Blood samples were collected over 36 d. Our results showed that the mean (+/-SD) area under the curve for the total serum response to [2H]retinol was 39.9 +/- 20.7 microg x d after the Golden Rice dose. Compared with that of the [13C10]retinyl acetate reference dose (84.7 +/- 34.6 microg x d), Golden Rice beta-carotene provided 0.24-0.94 mg retinol. Thus, the conversion factor of Golden Rice beta-carotene to retinol is 3.8 +/- 1.7 to 1 with a range of 1.9-6.4 to 1 by weight, or 2.0 +/- 0.9 to 1 with a range of 1.0-3.4 to 1 by moles. Beta-carotene derived from Golden Rice is effectively converted to vitamin A in humans. This trial was registered at clinicaltrials.gov as NCT00680355.

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gandhi, Diksha; Schmidt, Taly Gilat, E-mail: taly.gilat-schmidt@marquette.edu; Crotty, Dominic J.

Purpose: This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Methods: Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings.more » Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. Results: ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%–20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. Conclusions: ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.« less

A noise power spectrum study of a new model‐based iterative reconstruction system: Veo 3.0

PubMed Central

Li, Guang; Liu, Xinming; Dodge, Cristina T.; Jensen, Corey T.

2016-01-01

The purpose of this study was to evaluate performance of the third generation of model‐based iterative reconstruction (MBIR) system, Veo 3.0, based on noise power spectrum (NPS) analysis with various clinical presets over a wide range of clinically applicable dose levels. A CatPhan 600 surrounded by an oval, fat‐equivalent ring to mimic patient size/shape was scanned 10 times at each of six dose levels on a GE HD 750 scanner. NPS analysis was performed on images reconstructed with various Veo 3.0 preset combinations for comparisons of those images reconstructed using Veo 2.0, filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASiR). The new Target Thickness setting resulted in higher noise in thicker axial images. The new Texture Enhancement function achieved a more isotropic noise behavior with less image artifacts. Veo 3.0 provides additional reconstruction options designed to allow the user choice of balance between spatial resolution and image noise, relative to Veo 2.0. Veo 3.0 provides more user selectable options and in general improved isotropic noise behavior in comparison to Veo 2.0. The overall noise reduction performance of both versions of MBIR was improved in comparison to FBP and ASiR, especially at low‐dose levels. PACS number(s): 87.57.‐s, 87.57.Q‐, 87.57.C‐, 87.57.nf, 87.57.C‐, 87.57.cm PMID:27685118

SU-F-T-325: On the Use of Bolus in Dosimetry and Dose Reduction for Pacemaker and Defibrillator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, W; Kenneth, R; Higgins, S

Purpose: Special attention is required in planning and administering radiation therapy to patients with cardiac implantable electronic devices (CIEDs), such as pacemaker and defibrillator. The range of dose to CIEDs that can induce malfunction is very large among CIEDs. Significant defects have been reported at dose as low as 0.15Gy. Failures causing discomfort have been reported at dose as low as 0.05Gy. Therefore, accurate estimation of dose to CIED and dose reduction are both important even if the dose is expected to be less than the often-used 2Gy limit. We investigate the use of bolus in in vivo dosimetry formore » CIEDs. Methods: In our clinic, high-energy beams (>10MV) are not used for patients with CIED due to neutron production. Solid water phantom measurements of out-of-field dose for a 6MV beam were performed using parallel plate chamber at different depth with and without 2cm bolus covering the chamber. In vivo dosimetry at skin surface above the pacemaker was performed with and without bolus for 3 patients with pacemaker <5cm from the field edge. Results: Chamber measured dose at depth ∼1 to 1.5cm below the skin surface, where the CIED is normally located, was reduced by ∼6% – 20% with bolus. The dose reduction became smaller at deeper depth. In vivo dosimetry at skin surface also yielded ∼20% – 60% lower dose when using bolus for the 3 patients. In general, TPS calculation underestimated the dose. The dose measured with bolus is closer to the dose at the depth of the pacemaker and less affected by contaminant electrons and linac head leakage. Conclusion: In vivo CIED dose measurements should be performed with 1 to 2cm bolus covering the dosimeter on the skin above the CIED for more accurate CIED dose estimation. The use of bolus also reduces the dose delivered to CIED.« less

Dosimetric comparison between model 9011 and 6711 sources in prostate implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hualin, E-mail: zhang248@iupui.edu; Arizona Oncology Services, Phoenix, AZ; Beyer, David

2013-07-01

The purpose of this work is to evaluate the model 9011 iodine-125 ({sup 125}I) in prostate implants by comparing dosimetric coverage provided by the 6711 vs 9011 source implants. Postimplant dosimetry was performed in 18 consecutively implanted patients with prostate cancer. Two were implanted with the 9011 source and 16 with the 6711 source. For purposes of comparison, each implant was then recalculated assuming use of the other source. The same commercially available planning system was used and the specific source data for both 6711 and 9011 products were entered. The results of these calculations are compared side by sidemore » in the terms of the isodose values covering 100% (D100) and 90% (D90) of prostate volume, and the percentages of volumes of prostate, bladder, rectum, and urethra covered by 200% (V200), 150% (V150), 100% (V100), 50% (V50), and 20% (V20) of the prescribed dose as well. The 6711 source data overestimate coverage by 6.4% (ranging from 4.9% to 6.9%; median 6.6%) at D100 and by 6.6% (ranging from 6.2% to 6.8%; median 6.6%) at D90 compared with actual 9011 data. Greater discrepancies of up to 67% are seen at higher dose levels: average reduction for V100 is 2.7% (ranging from 0.6% to 7.7%; median 2.3%), for V150 is 14.6% (ranging from 6.1% to 20.5%; median 15.3%), for V200 is 14.9% (ranging from 4.8% to 19.1%; median 16%); similarly seen in bladder, rectal, and urethral coverage. This work demonstrates a clear difference in dosimetric behavior between the 9011 and 6711 sources. Using the 6711 source data for 9011 source implants would create a pronounced error in dose calculation. This study provides evidence that the 9011 source can provide the same dosimetric quality as the 6711 source, if properly used; however, the 6711 source data should not be considered as a surrogate for the 9011 source implants.« less

Phase 2 Trial of Hypofractionated High-Dose Intensity Modulated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Newly Diagnosed Glioblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iuchi, Toshihiko, E-mail: tiuchi@chiba-c.jp; Hatano, Kazuo; Kodama, Takashi

Purpose/Objectives: To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM). Methods and Materials: All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured. PTV1 was the surgical cavity and residual tumor on T1-weighted magnetic resonance images with 5-mm margins, PTV2 was the area with 15-mm margins surrounding the PTV1, and PTV3 was the high-intensity area on fluid-attenuated inversion recovery images. Irradiation was performed in 8 fractions at total doses of 68, 40, and 32 Gy formore » PTV1, PTV2, and PTV3, respectively. Concurrent TMZ was given at 75 mg/m{sup 2}/day for 42 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m{sup 2}/day for 5 days every 28 days. Overall and progression-free survivals were evaluated. Results: No acute IMRT-related toxicity was observed. The dominant posttreatment failure pattern was dissemination. During a median follow-up time of 16.3 months (range, 4.3-80.8 months) for all patients and 23.7 months (range, 12.4-80.8 months) for living patients, the median overall survival was 20.0 months after treatment. Radiation necrosis was diagnosed in 20 patients and was observed not only in the high-dose field but also in the subventricular zone (SVZ). Necrosis in the SVZ was significantly correlated with prolonged survival (hazard ratio, 4.08; P=.007) but caused deterioration in the performance status of long-term survivors. Conclusions: Hypofractionated high-dose IMRT with concurrent and adjuvant TMZ altered the dominant failure pattern from localized to disseminated and prolonged the survival of patients with GBM. Necrosis in the SVZ was associated with better patient survival, but the benefit of radiation to this area remains controversial.« less

Treatment of prednisolone-induced hyperglycaemia in hospitalized patients: Insights from a randomized, controlled study.

PubMed

Radhakutty, Anjana; Stranks, Jessica L; Mangelsdorf, Brenda L; Drake, Sophie M; Roberts, Gregory W; Zimmermann, Anthony T; Stranks, Stephen N; Thompson, Campbell H; Burt, Morton G

2017-04-01

Prednisolone causes hyperglycaemia predominantly between midday and midnight. Consequently, glargine-based basal-bolus insulin regimens may under treat daytime hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen is safer and more effective than a glargine-based regimen in hospitalized patients. Fifty inpatients prescribed ≥20 mg/day prednisolone acutely with (1) finger prick blood glucose level (BGL) ≥15 mmol/L or (2) BGLs ≥10 mmol/L within the previous 24 hours were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg bodyweight or 130% of the current daily insulin dose. Glycaemic control was assessed using a continuous glucose monitoring system. On Day 1, there were no significant differences in percentage of time outside a target glucose range of 4 to 10 mmol/L (41.3% ± 5.5% vs 50.0% ± 5.7%, P  = .28), mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/L, P  = .57) or glucose <4 mmol/L (2.2% ± 1.1% vs 2.0% ± 1.3%, P  = .92) in patients randomized to isophane and glargine. In patients treated for 3 days, the prednisolone dose was reduced ( P  = .02) and the insulin dose was increased over time ( P  = .02), but the percentage of time outside the 4 to 10 mmol/L glucose range did not differ over time ( P  = .45) or between groups ( P  = .24). There were no differences in the efficacy or safety of the isophane and glargine-based insulin regimens. We recommend an initial daily insulin dose of 0.5 units/kg bodyweight if not on insulin, a greater than 30% increase in pre-prednisolone insulin dose and larger insulin dose adjustments in patients with prednisolone-induced hyperglycaemia. © 2016 John Wiley & Sons Ltd.

Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.

PubMed

van der Heijde, Désirée; Deodhar, Atul; Wei, James C; Drescher, Edit; Fleishaker, Dona; Hendrikx, Thijs; Li, David; Menon, Sujatha; Kanik, Keith S

2017-08-01

To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Patient-specific quality assurance for the delivery of 60Co intensity modulated radiation therapy subject to a 0.35 T lateral magnetic field

PubMed Central

Li, H. Harold; Rodriguez, Vivian L.; Green, Olga L.; Hu, Yanle; Kashani, Rojano; Wooten, H. Omar; Yang, Deshan; Mutic, Sasa

2014-01-01

Purpose This work describes a patient-specific dosimetry quality assurance (QA) program for intensity modulated radiation therapy (IMRT) using ViewRay, the first commercial magnetic resonance imaging guided radiation therapy device. Methods and materials The program consisted of the following components: 1) one-dimensional multipoint ionization chamber measurement using a customized 15 cm3 cubic phantom, 2) two-dimensional (2D) radiographic film measurement using a 30×30×20 cm3 phantom with multiple inserted ionization chambers, 3) quasi- three-dimensional (3D) diode array (ArcCHECK) measurement with a centrally inserted ionization chamber, 4) 2D fluence verification using machine delivery log files, and 5) 3D Monte-Carlo (MC) dose reconstruction with machine delivery files and phantom CT. Results The ionization chamber measurements agreed well with treatment planning system (TPS) computed doses in all phantom geometries where the mean difference (mean ± SD) was 0.0% ± 1.3% (n=102, range, −3.0 % to 2.9%). The film measurements also showed excellent agreement with the TPS computed 2D dose distributions where the mean passing rate using 3% relative/3 mm gamma criteria was 94.6% ± 3.4% (n=30, range, 87.4% to 100%). For ArcCHECK measurements, the mean passing rate using 3% relative/3 mm gamma criteria was 98.9% ± 1.1% (n=34, range, 95.8% to 100%). 2D fluence maps with a resolution of 1×1 mm2 showed 100% passing rates for all plan deliveries (n=34). The MC reconstructed doses to the phantom agreed well with planned 3D doses where the mean passing rate using 3% absolute/3 mm gamma criteria was 99.0% ± 1.0% (n=18, range, 97.0% to100%), demonstrating the feasibility of evaluating the QA results in the patient geometry. Conclusions We have developed a dosimetry program for ViewRay’s patient-specific IMRT QA. The methodology will be useful for other ViewRay users. The QA results presented here can assist the RT community to establish appropriate tolerance and action limits for ViewRay’s IMRT QA. PMID:25442343

Evaluation on Geant4 Hadronic Models for Pion Minus, Pion Plus and Neutron Particles as Major Antiproton Annihilation Products

PubMed Central

Tavakoli, Mohammad Bagher; Mohammadi, Mohammad Mehdi; Reiazi, Reza; Jabbari, Keyvan

2015-01-01

Geant4 is an open source simulation toolkit based on C++, which its advantages progressively lead to applications in research domains especially modeling the biological effects of ionizing radiation at the sub-cellular scale. However, it was shown that Geant4 does not give a reasonable result in the prediction of antiproton dose especially in Bragg peak. One of the reasons could be lack of reliable physic model to predict the final states of annihilation products like pions. Considering the fact that most of the antiproton deposited dose is resulted from high-LET nuclear fragments following pion interaction in surrounding nucleons, we reproduced depth dose curves of most probable energy range of pions and neutron particle using Geant4. We consider this work one of the steps to understand the origin of the error and finally verification of Geant4 for antiproton tracking. Geant4 toolkit version 9.4.6.p01 and Fluka version 2006.3 were used to reproduce the depth dose curves of 220 MeV pions (both negative and positive) and 70 MeV neutrons. The geometry applied in the simulations consist a 20 × 20 × 20 cm3 water tank, similar to that used in CERN for antiproton relative dose measurements. Different physic lists including Quark-Gluon String Precompound (QGSP)_Binary Cascade (BIC)_HP, the recommended setting for hadron therapy, were used. In the case of pions, Geant4 resulted in at least 5% dose discrepancy between different physic lists at depth close to the entrance point. Even up to 15% discrepancy was found in some cases like QBBC compared to QGSP_BIC_HP. A significant difference was observed in dose profiles of different Geant4 physic list at small depths for a beam of pions. In the case of neutrons, large dose discrepancy was observed when LHEP or LHEP_EMV lists were applied. The magnitude of this dose discrepancy could be even 50% greater than the dose calculated by LHEP (or LHEP_EMV) at larger depths. We found that effect different Geant4 physic list in reproducing depth dose profile of the beam of pions was not negligible. Because the discrepancies were pronounced in smaller depth and also regarding the contribution of pions in deposited dose of a beam of antiproton, further investigation on choosing most suitable and accurate physic list for this purpose should be done. Furthermore, this study showed careful attention must be paid to choose the appropriate Geant4 physic list for neutron tracking depending to the applications criteria. We failed to find any agreement between results from Geant4 and Fluka to reproduce depth dose profile of pion with the energy range used in this study. PMID:26120569

Individual variations in dose response for spatial memory learning among outbred wistar rats exposed from 5 to 20 cGy of (56) Fe particles.

PubMed

Wyrobek, Andrew J; Britten, Richard A

2016-06-01

Exposures of brain tissue to ionizing radiation can lead to persistent deficits in cognitive functions and behaviors. However, little is known about the quantitative relationships between exposure dose and neurological risks, especially for lower doses and among genetically diverse individuals. We investigated the dose relationship for spatial memory learning among genetically outbred male Wistar rats exposed to graded doses of (56) Fe particles (sham, 5, 10, 15, and 20 cGy; 1 GeV/n). Spatial memory learning was assessed on a Barnes maze using REL3 ratios measured at three months after exposure. Irradiated animals showed dose-dependent declines in spatial memory learning that were fit by a linear regression (P for slope <0.0002). The irradiated animals showed significantly impaired learning at 10 cGy exposures, no detectable learning between 10 and 15 cGy, and worsened performances between 15 and 20 cGy. The proportions of poor learners and the magnitude of their impairment were fit by linear regressions with doubling doses of ∼10 cGy. In contrast, there were no detectable deficits in learning among the good learners in this dose range. Our findings suggest that genetically diverse individuals can vary substantially in their spatial memory learning, and that exposures at low doses appear to preferentially impact poor learners. This hypothesis invites future investigations of the genetic and physiological mechanisms of inter-individual variations in brain function related to spatial memory learning after low-dose HZE radiation exposures and to determine whether it also applies to physical trauma to brain tissue and exposures to chemical neurotoxicants. Environ. Mol. Mutagen. 57:331-340, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Evaluation of various approaches for assessing dose indicators and patient organ doses resulting from radiotherapy cone-beam CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rampado, Osvaldo, E-mail: orampado@cittadellasalute.to.it; Giglioli, Francesca Romana; Rossetti, Veronica

Purpose: The aim of this study was to evaluate various approaches for assessing patient organ doses resulting from radiotherapy cone-beam CT (CBCT), by the use of thermoluminescent dosimeter (TLD) measurements in anthropomorphic phantoms, a Monte Carlo based dose calculation software, and different dose indicators as presently defined. Methods: Dose evaluations were performed on a CBCT Elekta XVI (Elekta, Crawley, UK) for different protocols and anatomical regions. The first part of the study focuses on using PCXMC software (PCXMC 2.0, STUK, Helsinki, Finland) for calculating organ doses, adapting the input parameters to simulate the exposure geometry, and beam dose distribution inmore » an appropriate way. The calculated doses were compared to readouts of TLDs placed in an anthropomorphic Rando phantom. After this validation, the software was used for analyzing organ dose variability associated with patients’ differences in size and gender. At the same time, various dose indicators were evaluated: kerma area product (KAP), cumulative air-kerma at the isocenter (K{sub air}), cone-beam dose index, and central cumulative dose. The latter was evaluated in a single phantom and in a stack of three adjacent computed tomography dose index phantoms. Based on the different dose indicators, a set of coefficients was calculated to estimate organ doses for a range of patient morphologies, using their equivalent diameters. Results: Maximum organ doses were about 1 mGy for head and neck and 25 mGy for chest and pelvis protocols. The differences between PCXMC and TLDs doses were generally below 10% for organs within the field of view and approximately 15% for organs at the boundaries of the radiation beam. When considering patient size and gender variability, differences in organ doses up to 40% were observed especially in the pelvic region; for the organs in the thorax, the maximum differences ranged between 20% and 30%. Phantom dose indexes provided better correlation with organ doses than K{sub air} and KAP, with average ratios ranging between 0.9 and 1.1 and variations for different organs and protocols below 20%. The triple phantom setup allowed us to take into account scatter dose contributions, but nonetheless, the correlation with the evaluated organ doses was not improved with this method. Conclusions: The simulation of rotational geometry and of asymmetric beam distribution by means of PCXMC 2.0 enabled us to determine patient organ doses depending on weight, height and gender. Alternatively, the measurement of an in phantom dose indicator combined with proper correction coefficients can be a useful tool for a first dose estimation of in-field organs. The data and coefficients provided in this study can be applied to any patient undergoing a scan by an Elekta XVI equipment.« less

Phase I trial of volasertib, a Polo-like kinase inhibitor, plus platinum agents in solid tumors: safety, pharmacokinetics and activity.

PubMed

Awada, Ahmad; Dumez, Herlinde; Aftimos, Philippe G; Costermans, Jo; Bartholomeus, Sylvie; Forceville, Kathleen; Berghmans, Thierry; Meeus, Marie-Anne; Cescutti, Jessica; Munzert, Gerd; Pilz, Korinna; Liu, Dan; Schöffski, Patrick

2015-06-01

This trial evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and activity of volasertib, a selective Polo-like kinase 1 inhibitor that induces mitotic arrest and apoptosis, combined with cisplatin or carboplatin in patients with advanced/metastatic solid tumors (NCT00969761; 1230.6). Sequential patient cohorts (3 + 3 dose-escalation design) received a single infusion of volasertib (100-350 mg) with cisplatin (60-100 mg/m(2)) or carboplatin (area under the concentration versus time curve [AUC]4-AUC6) on day 1 every 3 weeks for up to six cycles. Sixty-one patients received volasertib/cisplatin (n = 30) or volasertib/carboplatin (n = 31) for a median of 3.5 (range, 1-6) and 2.0 (range, 1-6) treatment cycles, respectively. The most common cycle 1 dose-limiting toxicities (DLTs) were thrombocytopenia, neutropenia and fatigue. MTDs (based on cycle 1 DLTs) were determined to be volasertib 300 mg plus cisplatin 100 mg/m(2) and volasertib 300 mg plus carboplatin AUC6. Co-administration did not affect the pharmacokinetics of each drug. Partial responses were observed in two patients in each arm. Stable disease was achieved in 11 and six patients treated with volasertib/cisplatin and volasertib/carboplatin, respectively. Volasertib plus cisplatin or carboplatin at full single-agent doses was generally manageable and demonstrated activity in heavily pretreated patients with advanced solid tumors.

Comprehensive clinical commissioning and validation of the RayStation treatment planning system for proton therapy with active scanning and passive treatment techniques.

PubMed

Bäumer, C; Geismar, D; Koska, B; Kramer, P H; Lambert, J; Lemke, M; Plaude, S; Pschichholz, L; Qamhiyeh, S; Schiemann, A; Timmermann, B; Vermeren, X

2017-11-01

To commission the treatment planning system (TPS) RayStation for proton therapy including beam models for spot scanning and for uniform scanning. Tests consist of procedures from ESTRO booklet number 7, the German DIN for constancy checks of TPSs, and extra tests checking the dose perturbation function. The dose distributions within patients were verified in silico by a comparison of 65 clinical treatment plans with the TPS XiO. Dose-volume parameters, dose differences, and three-dimensional gamma-indices serve as measures of similarity. The monthly constancy checks of Raystation have been automatized with a script. The basic functionality of the software complies with ESTRO booklet number 7. For a few features minor enhancements are suggested. The dose distribution in RayStation agrees with the calculation in XiO. This is supported by a gamma-index (3mm/3%) pass rate of >98.9% (median over 59 plans) for the volume within the 20% isodose line and a difference of <0.3% of V 95 of the PTV (median over 59 plans). If spot scanning is used together with a range shifter, the dose level calculated by RayStation can be off by a few percent. RayStation can be used for the creation of clinical proton treatment plans. Compared to XiO RayStation has an improved modelling of the lateral dose fall-off in passively delivered fields. For spot scanning fields with range shifter blocks an empirical adjustment of monitor units is required. The computation of perturbed doses also allows the evaluation of the robustness of a treatment plan. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A Prospective Cohort Study of Gated Stereotactic Liver Radiation Therapy Using Continuous Internal Electromagnetic Motion Monitoring.

PubMed

Worm, Esben S; Høyer, Morten; Hansen, Rune; Larsen, Lars P; Weber, Britta; Grau, Cai; Poulsen, Per R

2018-06-01

Intrafraction motion can compromise the treatment accuracy in liver stereotactic body radiation therapy (SBRT). Respiratory gating can improve treatment delivery; however, gating based on external motion surrogates is inaccurate. The present study reports the use of Calypso-based internal electromagnetic motion monitoring for gated liver SBRT. Fifteen patients were included in a study of 3-fraction respiratory gated liver SBRT guided by 3 implanted electromagnetic transponders. The planning target volume was created by a 5-mm axial and 7-mm (n = 12) or 10-mm (n = 3) craniocaudal expansion of the clinical target volume (CTV) and covered with 67% of the prescribed CTV mean dose. Treatment was gated to the end-exhale phase of the respiratory cycle with beam-on when the target deviated <3 mm (left-right/anteroposterior) and 4 mm (craniocaudal) from the planned position, according to the monitored (25-Hz) transponder centroid position. The couch was adjusted remotely if baseline drifts >1 to 2 mm occurred. Log files of transponder motion were used to determine the geometric error and reconstruct the delivered CTV dose in the actual gated treatments and in simulated nongated treatments. No severe side effects were observed in relation to transponder implantation. All 45 treatment fractions were successfully guided using the Calypso system. The mean number of couch corrections during each gated fraction was 2.8 (range 0-7). The mean duty cycle during gated treatment was 62.5% (range 29.1%-84.9%). Without gating, the mean 3-dimensional geometric error during a fraction would have been 5.4 mm (range 2.7-12.1). Gating reduced this error to 2.0 mm (range 1.2-3.0). The patient mean reduction in minimum dose to 95% of the CTV relative to the planned dose was 6.0 percentage points (range 0.7-22.0) without gating and 0.8 percentage point (range 0.2-2.0) with gating. Gating using internal motion monitoring was successfully applied for liver SBRT. It markedly improved the geometric and dosimetric accuracy compared with nongated standard treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Dose delivered from Varian's CBCT to patients receiving IMRT for prostate cancer.

PubMed

Wen, Ning; Guan, Huaiqun; Hammoud, Rabih; Pradhan, Deepak; Nurushev, T; Li, Shidong; Movsas, Benjamin

2007-04-21

With the increased use of cone beam CT (CBCT) for daily patient setup, the accumulated dose from CBCT may be significantly higher than that from simulation CT or portal imaging. The objective of this work is to measure the dose from daily pelvic scans with fixed technical settings and collimations. CBCT scans were acquired in half-fan mode using a half bowtie and x-rays were delivered in pulsed-fluoro mode. The skin doses for seven prostate patients were measured on an IRB-approved protocol. TLD capsules were placed on the patient's skin at the central axis of three beams: AP, left lateral (Lt Lat) and right lateral (Rt Lat). To avoid the ring artefacts centred in the prostate, the treatment couch was dropped 3 cm from the patient's tattoo (central axis). The measured AP skin doses ranged 3-6 cGy for 20-33 cm separation. The larger the patient size the less the AP skin dose. Lateral doses did not change much with patient size. The Lt Lat dose was approximately 4.0 cGy, which was approximately 40% higher than the Rt Lat dose of approximately 2.6 cGy. To verify this dose asymmetry, surface doses on an IMRT QA phantom (oval shaped, 30 cm x 20 cm) were measured at the same three sites using TLD capsules with 3 cm table-drop. The dose asymmetry was due to: (1) kV source rotation which always starts from the patient's Lt Lat and ends at Lt Lat. Gantry rotation gets much slower near the end of rotation but dose rate stays constant and (2) 370 degrees scan rotation (10 degrees scan overlap on the Lt Lat side). In vivo doses were measured inside a Rando pelvic heterogeneous phantom using TLDs. The left hip (femoral head and neck) received the highest doses of approximately 10-11 cGy while the right hip received approximately 6-7 cGy. The surface and in vivo doses were also measured for phantoms at the central-axis setup. The difference was less than approximately 12% to the table-drop setup.

Dose delivered from Varian's CBCT to patients receiving IMRT for prostate cancer

NASA Astrophysics Data System (ADS)

Wen, Ning; Guan, Huaiqun; Hammoud, Rabih; Pradhan, Deepak; Nurushev, T.; Li, Shidong; Movsas, Benjamin

2007-04-01

With the increased use of cone beam CT (CBCT) for daily patient setup, the accumulated dose from CBCT may be significantly higher than that from simulation CT or portal imaging. The objective of this work is to measure the dose from daily pelvic scans with fixed technical settings and collimations. CBCT scans were acquired in half-fan mode using a half bowtie and x-rays were delivered in pulsed-fluoro mode. The skin doses for seven prostate patients were measured on an IRB-approved protocol. TLD capsules were placed on the patient's skin at the central axis of three beams: AP, left lateral (Lt Lat) and right lateral (Rt Lat). To avoid the ring artefacts centred in the prostate, the treatment couch was dropped 3 cm from the patient's tattoo (central axis). The measured AP skin doses ranged 3-6 cGy for 20-33 cm separation. The larger the patient size the less the AP skin dose. Lateral doses did not change much with patient size. The Lt Lat dose was ~4.0 cGy, which was ~40% higher than the Rt Lat dose of ~2.6 cGy. To verify this dose asymmetry, surface doses on an IMRT QA phantom (oval shaped, 30 cm × 20 cm) were measured at the same three sites using TLD capsules with 3 cm table-drop. The dose asymmetry was due to: (1) kV source rotation which always starts from the patient's Lt Lat and ends at Lt Lat. Gantry rotation gets much slower near the end of rotation but dose rate stays constant and (2) 370° scan rotation (10° scan overlap on the Lt Lat side). In vivo doses were measured inside a Rando pelvic heterogeneous phantom using TLDs. The left hip (femoral head and neck) received the highest doses of ~10-11 cGy while the right hip received ~6-7 cGy. The surface and in vivo doses were also measured for phantoms at the central-axis setup. The difference was less than ~12% to the table-drop setup.

Genetic effects on heavy ions in drosophila

NASA Technical Reports Server (NTRS)

Kale, P. G.

1986-01-01

Drosophila sex-linked recessive lethal mutation test was used to study the dose response relation and relative biological effectiveness of heavy ions. The experiments were performed using the heavy ion beams at BEVALAC of Lawrence Berkeley Laboratory. These experiments were undertaken according to the proposed milestones and included Ne-20, A-40 and Fe-65 ions with respective energies of 600 MeV, 840 MeV and 850 MeV. At these energies several doses of these radiations ranging from 20 to 1280 R were used. Space radiation exposure to astronauts is supposed to be quite low and therefore very low dose experiments i.e., 20 R, were also performed for the three ions. The mutation response was measured in all germ cell types i.e., spermatozoa, spermatids, spermatocytes and spermatogonia of treated Drosophila males. A linear dose frequency relation was observed for most of the range except at high doses where the saturation effect was observed. Also, a very significant difference was observed among the sensitivity of the four germ cell stages where spermatozoa and spermatids were more sensitive. At the higher doses of this range, most of the spermatogonia and spermatocytes were killed. Although comparative and identical experiments with X-rays or neutrons have not been performed, the compassion of our data with the ones available in literature suggest that the heavy ions have a high rbe and that they are several times more effective than low LET X-rays. The rbe compared to neutrons however appears to be only slightly higher.

Oral and Inactivated Poliovirus Vaccines in the Newborn: A review

PubMed Central

Mateen, Farrah J.; Shinohara, Russell T.; Sutter, Roland W.

2015-01-01

Background Oral poliovirus vaccine (OPV) remains the vaccine-of-choice for routine immunization and supplemental immunization activities (SIAs) to eradicate poliomyelitis globally. Recent data from India suggested lowerthanexpected immunogenicity of an OPV birth dose, prompting a review of the immunogenicity of OPV or inactivated poliovirus vaccine (IPV) when administered at birth. Methods We evaluated the seroconversion and reported adverse events among infants given a single birth dose (given ≤7 days of life) of OPV or IPV through a systematic review of published articles and conference abstracts from 1959-2011 in any language found on PubMed, Google Scholar, or reference lists of selected articles. Results 25 articles from 13 countries published between1959 and 2011 documented seroconversion rates in newborns following an OPV dose given within the first seven days of life. There were 10 studies that measured seroconversion rates between 4 and 8 weeks of a single birth dose of TOPV, using an umbilical cord blood draw at the time of birth to establish baseline antibody levels. The percentage of newborns who seroconverted at 8 weeks range 6-42% for poliovirus type 1, 2-63% for type 2, and 1-35% for type 3). For mOPV type 1, seroconversion ranged from 10-76%; mOPV type 3, the range was 12-58%; and for the one study reporting bOPV, it was 20% for type 1 and 7% for type 3. There were four studies of IPV in newborns with a seroconversion rate of 8-100% for serotype 1, 15-100% for serotype 2, and 15-94% for serotype 3, measured at 4-6 weeks of life. No serious adverse events related to newborn OPV or IPV dosing were reported, including no cases of acute flaccid paralysis. Conclusions There is great variability of the immunogenicity of a birth dose of OPV for reasons largely unknown. Our review confirms the utility of a birth dose of OPV, particularly in countries where early induction of polio immunity is imperative. IPV has higher seroconversion rates in newborns and may be a superior choice in countries which can afford IPV, but there have been studies of an IPV dose for newborns. PMID:22728224

Pineal tumors: analysis of treatment results in 20 patients.

PubMed

Amendola, Beatriz E; Wolf, Aizik; Coy, Sammie R; Amendola, Marco A; Eber, Daryl

2005-01-01

The authors evaluate their results when using gamma knife surgery (GKS) in the management of patients with tumors in the pineal region. This is a retrospective clinical evaluation of 20 patients with primary tumors of the pineal region treated with GKS from November 1994 through August 2003. There were 13 germ cell tumors, two pineoblastomas, two low-grade gliomas, one primitive neuroectodermal tumor, one teratoma, and one pineocytoma. There were 10 male and 10 female patients. Their median age was 15.5 years (range 5-71 years). The median margin dose was 11 Gy (range 8-20 Gy). The median target volume was 3.1 cm3 (range 0.1-49.9 cm3). Five patients received sequential systemic chemotherapy and four underwent adjuvant conventional radiation therapy. Seventeen (85%) of 20 patients are alive with a median survival of 30.4 months (range 0-85.7 months). Two patients required retreatment. Three patients died: one of unrelated causes, one who presented with extensive local disease, and the other of meningeal carcinomatosis with local control of the primary tumor. No complications from GKS were noted. This initial experience suggests that GKS is a valuable treatment modality for the management of pineal region tumors. This technique offers excellent local tumor control and minimal patient morbidity, allowing for immediate use of systemic chemotherapy and/or conventional radiation if indicated.

Assessing age-dependent susceptibility to measles in Japan.

PubMed

Kinoshita, Ryo; Nishiura, Hiroshi

2017-06-05

Routine vaccination against measles in Japan started in 1978. Whereas measles elimination was verified in 2015, multiple chains of measles transmission were observed in 2016. We aimed to reconstruct the age-dependent susceptibility to measles in Japan so that future vaccination strategies can be elucidated. An epidemiological model was used to quantify the age-dependent immune fraction using datasets of vaccination coverage and seroepidemiological survey. The second dose was interpreted in two different scenarios, i.e., booster and random shots. The effective reproduction number, the average number of secondary cases generated by a single infected individual, and the age at infection were explored using the age-dependent transmission model and the next generation matrix. While the herd immunity threshold of measles likely ranges from 90% to 95%, assuming that the basic reproductive number ranges from 10 to 20, the estimated immune fraction in Japan was below those thresholds in 2016, despite the fact that the estimates were above 80% for all ages. If the second dose completely acted as the booster shot, a proportion immune above 90% was achieved only among those aged 5years or below in 2016. Alternatively, if the second dose was randomly distributed regardless of primary vaccination status, a proportion immune over 90% was achieved among those aged below 25years. The effective reproduction number was estimated to range from 1.50 to 3.01 and from 1.50 to 3.00, respectively, for scenarios 1 and 2 in 2016; if the current vaccination schedule were continued, the reproduction number is projected to range from 1.50 to 3.01 and 1.39 to 2.78, respectively, in 2025. Japan continues to be prone to imported cases of measles. Supplementary vaccination among adults aged 20-49years would be effective if the chains of transmission continue to be observed in that age group. Copyright © 2017 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Merchant, Thomas E.; Gajjar, Amar

Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametricmore » maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in brainstem anisotropy may serve as an indicator of the recovery time trend over 5 years after radiation therapy.« less

Efficacy and optimal dose of daily polyethylene glycol 3350 for treatment of constipation and encopresis in children.

PubMed

Pashankar, D S; Bishop, W P

2001-09-01

To determine efficacy, safety, and optimal dose of a laxative, polyethylene glycol (PEG) 3350, in children with chronic constipation. Children with chronic constipation (n = 24) were treated with PEG for 8 weeks at an initial dose of 1 g/kg/d. The dose was adjusted every 3 days as required to achieve 2 soft stools per day. A diary was kept to monitor dose, stool frequency and consistency, soiling, and other symptoms. Stool consistency was rated from 1 (hard) to 5 (watery). Subjects were examined for fecal retention. The Student t test and the Fisher exact test were used for data analysis. All 20 children who completed the study found PEG to be palatable and were satisfied with the treatment. There were no significant adverse effects. Weekly stool frequency increased from 2.3 +/- 0.4 to 16.9 +/- 1.6 (P <.0001) during treatment and stool consistency from 1.2 +/- 0.1 to 3.3 +/- 0.1 (P <.0001). In 9 children with soiling, weekly soiling events declined from 10.0 +/- 2.4 to 1.3 +/- 0.7 (P =.003). The mean effective dose was 0.84 g/kg/d (range, 0.27-1.42 g/kg/d). Daily administration of PEG at a mean dose of 0.8 g/kg is an effective, safe, and palatable treatment for constipation.

On the development of a VIPARnd radiotherapy 3D polymer gel dosimeter

NASA Astrophysics Data System (ADS)

Kozicki, Marek; Jaszczak, Malwina; Maras, Piotr; Dudek, Mariusz; Cłapa, Marian

2017-02-01

This work presents an improvement of the VIPARnd (‘nd’ stands for ‘normoxic, double’, or VIP) polymer gel dosimeter. The gel composition was altered by increasing the concentration of the monomeric components, N-vinylpyrrolidone (NVP) and N,N‧-methylenebisacrylamide (MBA), in co-solvent solutions. The optimal composition (VIPARCT, where ‘CT’ stands for computed tomography, or VIC) comprised: 17% NVP, 8% MBA, 12% t-BuOH, 7.5% gelatine, 0.007% ascorbic acid, 0.0008% CuSO4  ×  5H2O and 0.02% hydroquinone. The following characteristics of VIC were achieved: (i) linear dose range of 0.9_30 Gy, (ii) saturation for radiation doses of over 50 Gy, (iii) threshold dose of about 0.5 Gy, (iv) dose sensitivity of 0.171 Gy-1 s-1, which is roughly 2.2 times higher than that of VIP (for nuclear magnetic resonance measurements). It was also found that VIC is dose- rate-independent, and its dose response does not alter if the radiation source is changed from electrons to photons for external beam radiotherapy. The gel responded similarly to irradiation with small changes in radiation energy but was sensitive to larger energy changes. The VIC gel retained temporal stability from 20 h until at least 10 d after irradiation, whereas spatial stability was retained from 20 h until at least 6 d after irradiation. The scheme adopted for VIC manufacturing yields repeatable gels in terms of radiation dose response. The VIC was also shown to perform better than VIP using x-ray computed tomography as a readout method; the dose sensitivity of VIC (0.397 HU Gy-1) was 1.5 times higher than that of VIP. Also, the dose resolution of VIC was better than that of VIP in the whole dose range examined.

Effective dose assessment in the maxillofacial region using thermoluminescent (TLD) and metal oxide semiconductor field-effect transistor (MOSFET) dosemeters: a comparative study

PubMed Central

Schulze, D; Wolff, J; Rottke, D

2014-01-01

Objectives: The objective of this study was to compare the performance of metal oxide semiconductor field-effect transistor (MOSFET) technology dosemeters with thermoluminescent dosemeters (TLDs) (TLD 100; Thermo Fisher Scientific, Waltham, MA) in the maxillofacial area. Methods: Organ and effective dose measurements were performed using 40 TLD and 20 MOSFET dosemeters that were alternately placed in 20 different locations in 1 anthropomorphic RANDO® head phantom (the Phantom Laboratory, Salem, NY). The phantom was exposed to four different CBCT default maxillofacial protocols using small (4 × 5 cm) to full face (20 × 17 cm) fields of view (FOVs). Results: The TLD effective doses ranged between 7.0 and 158.0 µSv and the MOSFET doses between 6.1 and 175.0 µSv. The MOSFET and TLD effective doses acquired using four different (FOV) protocols were as follows: face maxillofacial (FOV 20 × 17 cm) (MOSFET, 83.4 µSv; TLD, 87.6 µSv; −5%); teeth, upper jaw (FOV, 8.5 × 5.0 cm) (MOSFET, 6.1 µSv; TLD, 7.0 µSv; −14%); tooth, mandible and left molar (FOV, 4 × 5 cm) (MOSFET, 10.3 µSv; TLD, 12.3 µSv; −16%) and teeth, both jaws (FOV, 10 × 10 cm) (MOSFET, 175 µSv; TLD, 158 µSv; +11%). The largest variation in organ and effective dose was recorded in the small FOV protocols. Conclusions: Taking into account the uncertainties of both measurement methods and the results of the statistical analysis, the effective doses acquired using MOSFET dosemeters were found to be in good agreement with those obtained using TLD dosemeters. The MOSFET dosemeters constitute a feasible alternative for TLDs for the effective dose assessment of CBCT devices in the maxillofacial region. PMID:25143020

Clinical and Dosimetric Predictors of Radiation Pneumonitis in a Large Series of Patients Treated With Stereotactic Body Radiation Therapy to the Lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, Ryan; Han Gang; Sarangkasiri, Siriporn

2013-01-01

Purpose: To report clinical and dosimetric factors predictive of radiation pneumonitis (RP) in patients receiving lung stereotactic body radiation therapy (SBRT) from a series of 240 patients. Methods and Materials: Of the 297 isocenters treating 263 patients, 240 patients (n=263 isocenters) had evaluable information regarding RP. Age, gender, current smoking status and pack-years, O{sub 2} use, Charlson Comorbidity Index, prior lung radiation therapy (yes/no), dose/fractionation, V{sub 5}, V{sub 13}, V{sub 20}, V{sub prescription}, mean lung dose, planning target volume (PTV), total lung volume, and PTV/lung volume ratio were recorded. Results: Twenty-nine patients (11.0%) developed symptomatic pneumonitis (26 grade 2, 3more » grade 3). The mean V{sub 20} was 6.5% (range, 0.4%-20.2%), and the average mean lung dose was 5.03 Gy (0.547-12.2 Gy). In univariable analysis female gender (P=.0257) and Charlson Comorbidity index (P=.0366) were significantly predictive of RP. Among dosimetric parameters, V{sub 5} (P=.0186), V{sub 13} (P=.0438), and V{sub prescription} (where dose = 60 Gy) (P=.0128) were significant. There was only a trend toward significance for V{sub 20} (P=.0610). Planning target volume/normal lung volume ratio was highly significant (P=.0024). In multivariable analysis the clinical factors of female gender, pack-years smoking, and larger gross internal tumor volume and PTV were predictive (P=.0094, .0312, .0364, and .052, respectively), but no dosimetric factors were significant. Conclusions: Rate of symptomatic RP was 11%. Our mean lung dose was <600 cGy in most cases and V20 <10%. In univariable analysis, dosimetric factors were predictive, while tumor size (or tumor/lung volume ratio) played a role in multivariable and univariable and analysis, respectively.« less

Shelf life extension of minimally processed cabbage and cucumber through gamma irradiation.

PubMed

Khattak, Amal Badshah; Bibi, Nizakat; Chaudry, Muhammad Ashraf; Khan, Misal; Khan, Maazullah; Qureshi, Muhammad Jamil

2005-01-01

The influence of irradiation of minimally processed cabbage and cucumber on microbial safety, texture, and sensory quality was investigated. Minimally processed, polyethylene-packed, and irradiated cabbage and cucumber were stored at refrigeration temperature (5 degrees C) for 2 weeks. The firmness values ranged from 3.23 kg (control) to 2.82 kg (3.0-kGy irradiated samples) for cucumbers, with a gradual decrease in firmness with increasing radiation dose (0 to 3 kGy). Cucumbers softened just after irradiation with a dose of 3.0 kGy and after 14 days storage, whereas the texture remained within acceptable limits up to a radiation dose of 2.5 kGy. The radiation treatment had no effect on the appearance scores of cabbage; however, scores decreased from 7.0 to 6.7 during storage. The appearance and flavor scores of cucumbers decreased with increasing radiation dose, and overall acceptability was better after radiation doses of 2.5 and 3.0 kGy. The aerobic plate counts per gram for cabbage increased from 3 to 5 log CFU (control), from 1.85 to 2.93 log CFU (2.5 kGy), and from a few colonies to 2.6 log CFU (3.0 kGy) after 14 days of storage at 5 degrees C. A similar trend was noted for cucumber samples. No coliform bacteria were detected at radiation doses greater than 2.0 kGy in either cabbage or cucumber samples. Total fungal counts per gram of sample were within acceptable limits for cucumbers irradiated at 3.0 kGy, and for cabbage no fungi were detected after 2.0-kGy irradiation. The D-values for Escherichia coli in cucumber and cabbage were 0.19 and 0.17 kGy, and those for Salmonella Paratyphi A were 0.25 and 0.29 kGy for cucumber and cabbage, respectively.

Stereotactic radiosurgery for trigeminal pain secondary to recurrent malignant skull base tumors.

PubMed

Phan, Jack; Pollard, Courtney; Brown, Paul D; Guha-Thakurta, Nandita; Garden, Adam S; Rosenthal, David I; Fuller, Clifton D; Frank, Steven J; Gunn, G Brandon; Morrison, William H; Ho, Jennifer C; Li, Jing; Ghia, Amol J; Yang, James N; Luo, Dershan; Wang, He C; Su, Shirley Y; Raza, Shaan M; Gidley, Paul W; Hanna, Ehab Y; DeMonte, Franco

2018-04-27

OBJECTIVE The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors. METHODS From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15-20 Gy) prescribed to the 50% isodose line (range 43%-55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21-27 Gy) prescribed to the 50% isodose line (range 45%-50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS. RESULTS Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0-34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3-4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2-3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention. CONCLUSIONS GKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Efficacy of a dose range of simulated sunlight exposures in raising vitamin D status in South Asian adults: implications for targeted guidance on sun exposure.

PubMed

Farrar, Mark D; Webb, Ann R; Kift, Richard; Durkin, Marie T; Allan, Donald; Herbert, Annie; Berry, Jacqueline L; Rhodes, Lesley E

2013-06-01

Vitamin D is essential for bone health, and cutaneous synthesis is an important source. South Asians cannot attain adequate amounts of vitamin D by following general recommendations on summer sunlight exposure at northerly latitudes, and increased exposure may be appropriate for improving their vitamin D status. We examined the efficacy of a dose range of simulated summer sunlight exposures in raising vitamin D status in UK adults of South Asian ethnicity. In a dose-response study, healthy adults of South Asian ethnicity (n = 60; 20-60 y old) received 1 of 6 ultraviolet exposures ranging from 0.65 to 3.9 standard erythema doses (SEDs), which were equivalent to 15-90 min unshaded noontime summer sunlight at 53.5°N (Manchester, United Kingdom), 3 times/wk for 6 wk, while wearing casual clothes that revealed a 35% skin area. Serum 25-hydroxyvitamin D [25(OH)D] was measured weekly, and dietary vitamin D was estimated. At baseline, all completing participants (n = 51) were vitamin D insufficient [25(OH)D concentrations <20 ng/mL], and a high proportion of participants were deficient [35% of subjects had 25(OH)D concentrations <5 ng/mL, and 90% of subjects had 25(OH)D concentrations <10 ng/mL, which are concentrations at which osteomalacia and rickets occur). The 25(OH)D concentration rose significantly in all dose groups. Postcourse, all participants achieved 25(OH)D concentrations ≥5 ng/mL, whereas only 6 subjects attained 25(OH)D concentrations ≥20 ng/mL. Participants who received exposures ≥1.95 SEDs (equivalent to 45 min unshaded sunlight; n = 33) attained a mean (±SD) 25(OH)D concentration of 15.7 ± 5 ng/mL (mean rise: 8.7 ± 5.7 ng/mL; 95% CI: 6.8, 10.6 ng/mL; P < 0.001), and 94% of subjects achieved concentrations >10 ng/mL. Targeted guidance on sunlight exposure could usefully enhance vitamin D status to avoid deficiency [25(OH)D concentration >10 ng/mL] in South Asians living at latitudes distant from the equator. This trial was registered at the ISRCTN Register (www.isrctn.org) as 07565297.

Characterization of MOSFET dosimeters for low‐dose measurements in maxillofacial anthropomorphic phantoms

PubMed Central

Wolff, Jan E.; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-01-01

The aims of this study were to characterize reinforced metal‐oxide‐semiconductor field‐effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low‐dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50–90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point‐dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k=2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low‐dose limit. The sensitivity was 3.09±0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was −8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD‐comparable low‐dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the sensitivity is too low. PACS number: 87.50.wj PMID:26219008

SU-F-T-85: Energy Modulated Electron Postmastectomy Unreconstructed (PU) Chest Wall (CW) Irradiation Technique to Achieve Heart Sparing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, L; Ballangrud, A; Mechalakos, J

Purpose: For left-sided PU patients requiring CW and nodal irradiation, sometimes partial wide tangents (PWT) are not feasible due to abnormal chest wall contour or heart position close to the anterior chest wall or unusual wide excision scar. We developed an energy modulated electron chest wall irradiation technique that will achieve heart sparing. Methods: Ten left-sided PU patients were selected for this dosimetry study. If PWT were used, the amount of the ipsilateral lung would be ranged 3.4 to 4.4 cm, and the amount of heart would be ranged 1.3 to 3.8 cm. We used electron paired fields that matchedmore » on the skin to achieve dose conformity to the chest wall. The enface electron fields were designed at extended SSD from a single isocenter and gantry angle with different energy beams using different cutout. Lower energy was used in the central chest wall part and higher energy was used in the periphery of the chest wall. Bolus was used for the electron fields to ensure adequate skin dose coverage. The electron fields were matched to the photon supra-clavicle field in the superior region. Daily field junctions were used to feather the match lines between all the fields. Target volumes and normal tissues were drawn according to institutional protocols. Prescription dose was 2Gy per fraction for a total 50Gy. Dose calculations were done with Eclipse EMC-11031 for Electron and AAA-11031 for photons. Results: Six patients were planned using 6/9MeV, three using 9/12MeV and one 6/12MeV. Target volumes achieved adequate coverage. For heart, V30Gy, V20Gy and Mean Dose were 0.6%±0.6%, 2.7%±1.7%, and 3.0Gy±0.8Gy respectively. For ipsilateral lung, V50Gy, V20Gy, V10Gy and V5Gy were 0.9%±1.1%, 34.3%±5.1%, 51.6%±6.3% and 64.1%±7.5% respectively. Conclusion: For left-sided PU patients with unusual anatomy, energy modulated electron CW irradiation technique can achieve heart sparing with acceptable lung dose.« less

Results of multifield conformal radiation therapy of nonsmall-cell lung carcinoma using multileaf collimation beams.

PubMed

Bahri, S; Flickinger, J C; Kalend, A M; Deutsch, M; Belani, C P; Sciurba, F C; Luketich, J D; Greenberger, J S

1999-01-01

A five-field conformal technique with three-dimensional radiation therapy treatment planning (3-DRTP) has been shown to permit better definition of the target volume for lung cancer, while minimizing the normal tissue volume receiving greater than 50% of the target dose. In an initial study to confirm the safety of conventional doses, we used the five-field conformal 3-DRTP technique. We then used the technique in a second study, enhancing the therapeutic index in a series of 42 patients, as well as to evaluate feasibility, survival outcome, and treatment toxicity. Forty-two consecutive patients with nonsmall-cell lung carcinoma (NSCLC) were evaluated during the years 1993-1997. The median age was 60 years (range 34-80). The median radiation therapy (RT) dose to the gross tumor volume was 6,300 cGy (range 5,000-6,840 cGy) delivered over 6 to 6.5 weeks in 180-275 cGy daily fractions, 5 days per week. There were three patients who received a split course treatment of 5,500 cGy in 20 fractions, delivering 275 cGy daily with a 2-week break built into the treatment course after 10 fractions. The stages of disease were II in 2%, IIIA in 40%, IIIB in 42.9%, and recurrent disease in 14.3% of the patients. The mean tumor volume was 324.14 cc (range 88.3-773.7 cc); 57.1% of the patients received combined chemoradiotherapy, while the others were treated with radiation therapy alone. Of the 42 patients, 7 were excluded from the final analysis because of diagnosis of distant metastasis during treatment. Two of the patients had their histology reinterpreted as being other than NSCLC, 2 patients did not complete RT at the time of analysis, and 1 patient voluntarily discontinued treatment because of progressive deterioration. Median follow-up was 11.2 months (range 3-32.5 months). Survival for patients with Stage III disease was 70.2% at 1 year and 51.5% at 2 years, with median survival not yet reached. Local control for the entire series was 23.3+/-11.4% at 2 years. However, for Stage III patients, local control was 50% at 1 year and 30% at 2 years. Patients who received concurrent chemotherapy had significantly improved survival (P = 0.002) and local control (P = 0.004), compared with RT alone. Late esophageal toxicity of > or =Grade 3 occurred in 14.1+/-9.3% of patients (3 of 20) receiving combined chemoradiotherapy, but in none of the 15 patients treated with RT alone. Pulmonary toxicity limited to Grades 1-2 occurred in 6.8% of the patients, and none developed > or =Grade 3 pulmonary toxicity. Patients with locally advanced NSCLC, who commonly have tumor volumes in excess of 200 cc, presenta challenge for adequate dose delivery without significant toxicity. Our five-field conformal 3-DRTP technique, which incorporates treatment planning by dose/volume histogram (DVH) was associated with minimal toxicity and may facilitate dose escalation to the gross tumor.

Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

PubMed

Viscardi, Rose M; Othman, Ahmed A; Hassan, Hazem E; Eddington, Natalie D; Abebe, Elias; Terrin, Michael L; Kaufman, David A; Waites, Ken B

2013-05-01

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial clearance, but the effect on BPD remains to be determined.

Azithromycin To Prevent Bronchopulmonary Dysplasia in Ureaplasma-Infected Preterm Infants: Pharmacokinetics, Safety, Microbial Response, and Clinical Outcomes with a 20-Milligram-per-Kilogram Single Intravenous Dose

PubMed Central

Othman, Ahmed A.; Hassan, Hazem E.; Eddington, Natalie D.; Abebe, Elias; Terrin, Michael L.; Kaufman, David A.; Waites, Ken B.

2013-01-01

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)0.75 [WT(kg)0.75 indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)0.75; central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial clearance, but the effect on BPD remains to be determined. PMID:23439637

SU-F-207-14: Low Contrast Detectability (LCD) at Different Diagnostic Reference Levels for Adult Abdominal CT Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahmood, U; Erdi, Y

2015-06-15

Purpose Using diagnostic reference levels (DRL) to optimize CT protocols has potential to reduce radiation dose and meet regulatory requirements. However, DRL’s tend to be misconstrued as dose limits, are typically designed for specific patient populations, and are assumed to have acceptable image quality (AIQ) associated with them. To determine the image quality that is associated with established DRL’s for adult abdominal CT studies, a LCD phantom study was employed. Methods: A CT phantom (CIRS) containing three columns of 7 spherical targets, ranging from 10mm to 2.4 mm, that are 5, 10, and 20 HU below the background (HUBB) matrixmore » was scanned with a GE HD750 64 slice scanner. The phantom was scanned at the NEXT 2006 25th CTDIvol of 12 mGy, the NCRP 172 achievable dose (AD) CTDIvol of 17 mGy and 75th CTDIvol of 25 mGy and at the ACR recommended CTDIvol of 25 mGy. It was also scanned at a CTDIvol 20% greater than the AD at 20 mGy and the ACR maximum threshold of 30 mGy. Results: At the NEXT 2006 25th percentile CTDIvol of 12 mGy, a 6.3 mm low contrast lesion was detectable in the 20 HUBB; 6.3 mm in the 10 HUBB and 10 mm in the 5 HUBB column. Increasing the CTDIvol to the NCRP 172 AD of 17 mGy, an additional 4.8 mm lesion was visualized in the 20 HUBB column. At 20 mGy, an additional 4.8 mm lesion was detectable in the 10 HUBB column. No further lesions were visible between 20 and 30 mGy. However, conspicuity of all lesions increased with each additional step up in CTDI. Conclusion: Optimizing radiation dose to achieve AIQ is a critical aspect of any dose optimization committee. Hence, judicious monitoring of radiation exposure to patients has to be balanced with diagnostic image quality.« less

Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Eugene; Corbett, James R.; Moran, Jean M.

Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses tomore » the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.« less

An 11-year review of levetiracetam ingestions in children less than 6 years of age.

PubMed

Lewis, J C; Albertson, T E; Walsh, M J

2014-11-01

Levetiracetam is a new anticonvulsant, which works to block high-voltage-activated Ca(++) channels in children, for partial-onset seizures. Reports of clinical experience with pediatric ingestions are minimal. The purpose of this study was to characterize the toxicity of accidental levetiracetam exposures in children less than 6 years of age. This was an 11-year retrospective observational case series of pediatric (< 6 years old) levetiracetam ingestions reported to a Poison Control System from 2002 to 2013. Case narratives were individually reviewed to collect desired information on exposure and clinical course. Inclusion criteria were levetiracetam as a single ingested medication, age less than 6 years, treatment in a health care facility, and followed to a known outcome. Eighty-two cases met inclusion criteria with 55% female patients and overall median age of 2.0 years (range: 1-60 months). The levetiracetam dose ingested was reported in 69 (84.1%) cases, with exact dose (median dose, 45.0 mg/kg; range, 10.5-1429 mg/kg) reported in 33 cases (40.2%). Of these, twenty-nine cases (88%) involved the oral solution formulation and 28 cases (85%) had unintentional therapeutic error as the cause of the exposure. No dose-response relationship was demonstrated; however, the odds of a levetiracetam-naive patient, (median dose, 26.9 mg/kg; N = 15) with an unintentional exposure, developing drowsiness or ataxia was 6 times that of a patient who was not naïve to levetiracetam (median dose, 70.1 mg/kg; N = 20) (Odds ratio [OR], 6.0; 95% confidence interval [CI], 1.03-35.91).Of the 82 cases, 17 (20.7%) developed untoward clinical effects of drowsiness and/or ataxia. Eighty patients (97.6%) were treated and discharged from the emergency department, and two patients (2.4%) were admitted. The two patients admitted included a two-month old who was accidentally given a dose 10 times that of her usual dose and a 3-year old who was lethargic on arrival to the hospital after ingestion of an unknown dose. Of all patients, 66 patients (80.5%) had no effect from the drug exposure. The medical outcome was considered to be minor in 15 cases (18.3%), and moderate in 1 case (1.2%). There were no cases with major outcomes and no deaths. Pediatric levetiracetam exposures were associated with few transient clinical effects. Poison Control Centers may wish to consider acuity of ingestion when developing send-in protocols.

Antibacterial activity of the emerging Fusarium mycotoxins enniatins A, A₁, A₂, B, B₁, and B₄ on probiotic microorganisms.

PubMed

Roig, M; Meca, G; Marín, R; Ferrer, E; Mañes, J

2014-07-01

Enniatins (ENs) are secondary metabolites produced by several Fusarium strains, chemically characterized as N-methylated cyclohexadepsipeptides. These compounds are known to act as antifungal and antibacterial agents, but they also possess anti-insect and phytotoxic properties. In this study, the antimicrobial effect of pure fractions of the bioactive compounds ENs A, A₁, A₂, B, B₁, and B₄ was tested towards nine probiotic microrganisms, twenty-two Saccharomyces cerevisiae strains and nine Bacillus subtilis strains. Antimicrobial analyses were carried out the disc-diffusion method using ENs concentrations ranging from 0.2 to 20,000 ng. Plates were incubated for 24 h at 37 °C before reading the diameter of the inhibition spots. ENs A, A₁, A₂, B, B₁ and B₄, were active against several microorganisms with inhibition halos ranging from 3 to 12 mm in diameter. The most active mycotoxin was the EN A₁, which reduced the microbial growth of 8 strains at the dose of 20,000 ng, with inhibition spots sized between 8 and 12 mm. ENs B and B₄ showed no antimicrobial activity towards the microorganisms tested at doses up to 20,000 ng per disc. Copyright © 2014 Elsevier Ltd. All rights reserved.

Proposed linear energy transfer areal detector for protons using radiochromic film.

PubMed

Mayer, Rulon; Lin, Liyong; Fager, Marcus; Douglas, Dan; McDonough, James; Carabe, Alejandro

2015-04-01

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured at a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%-10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%-15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuazon, B; Narayanasamy, G; Kirby, N

Purpose: The purpose of this study was to evaluate and compare the accuracy of dose calculation algorithms in the second check software programs Radcalc, Diamond, IMSure, and MUcheck, against the Pinnacle3 treatment planning system (TPS). Methods: Baseline accuracy of the second check software was established by comparison against Pinnacle TPS data using open square fields of 5, 10, 20, 30 and 40cm in a SAD setup. 18 previously treated patients’ files were exported from the Pinnacle3 TPS to each of the four second check softwares, consisting of 146 step and shoot intensity modulated radiotherapy (IMRT) beams and 60 Smart Arcs.more » Monitor unit (MU) calculated in each of the software were compared with the TPS and the values were represented as a percent difference. Open fields were calculated as a baseline for each software’s accuracy using 5×5, 10×10, 20×20, 30×30, and 40×40 fields. Box plots, Pearson correlation, and Bland-Altman analysis were used for comparison of the results. Results: The baseline accuracy was established to within 0.6%, −1.4%, −0.2%, and −1.0% for Diamond, IMSure,MUcheck, and Radcalc, respectively. In the clinical data, the dose difference represented as mean ± 1 standard deviation were 0.7%±0.1%, −0.3%±0.1%, −1.5%±0.1%, and 0.4%±0.0% for Diamond, IMSure, MUcheck, and Radcalc, respectively Conclusion: The implementation of Clarkson algorithm for the dose calculation between each of the software in question can vary considerably. The currently used second check software, Radcalc has shown the best agreement on average, variance, and smallest percent range from Pinnacle3 TPS values. The closest in average percent difference from the TPS data was the IMSure software, but has significantly larger variance and percent range. The mean percent differences in Diamond and MUcheck were significantly larger than Radcalc and IMSure.« less

Estimated UV doses to psoriasis patients during climate therapy at Gran Canaria in March 2006

NASA Astrophysics Data System (ADS)

Nilsen, L. T. N.; Søyland, E.; Krogstad, A. L.

2008-01-01

Psoriasis is a chronic inflammatory disease involving about 2-3% of the Norwegian population. Sun exposure has a positive effect on most psoriasis lesions, but ultraviolet (UV) radiation also causes a direct DNA damage in the skin cells and comprises a carcinogenic potential. UV exposure on the skin causes a local as well as a systemic immune suppressive effect, but the relation between sun exposure and these biological effects is not well known. In March 2006 a study was carried out to investigate possible therapeutic outcome mechanisms in 20 psoriasis patients receiving climate therapy at Gran Canaria. This paper presents estimates of their individual skin UV-doses based on UV measurements and the patients' diaries with information on time spent in the sun. On the first day of exposure the patients received on average 5.1 Standard Erythema Doses (SED: median=4.0 SED, range 2.6-10.3 SED) estimated to the skin. During the 15 days study they received 165.8 SED (range 104.3-210.1 SED). The reduction in PASI score was 72.8% on average, but there was no obvious relation between the improvement and the UV dose. The UV doses were higher than those found from climate therapy studies at other locations. It seems beneficial to use more strict exposure schedules that consider the available UV irradiance, depending on time of the day, time of the year and weather conditions.

Advanced techniques in neoadjuvant radiotherapy allow dose escalation without increased dose to the organs at risk : Planning study in esophageal carcinoma.

PubMed

Fakhrian, K; Oechsner, M; Kampfer, S; Schuster, T; Molls, M; Geinitz, H

2013-04-01

The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive ≥ 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher doses through advanced techniques in the neoadjuvant treatment of LAEC.

Pharmacokinetics of Venetoclax, a Novel BCL-2 Inhibitor, in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma.

PubMed

Salem, Ahmed Hamed; Agarwal, Suresh K; Dunbar, Martin; Enschede, Sari L Heitner; Humerickhouse, Rod A; Wong, Shekman L

2017-04-01

Venetoclax is a selective BCL-2 inhibitor that is approved in the United States for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least 1 prior therapy. The aim of this analysis was to characterize venetoclax pharmacokinetics in the plasma and urine of patients with hematological malignancies and evaluate the effect of dose proportionality, accumulation, weak and moderate CYP3A inhibitors, as well as low- and high-fat meals on venetoclax pharmacokinetics. Patients received a once-daily venetoclax dose of 20 to 1200 mg. Pharmacokinetic parameters were estimated using noncompartmental methods. Venetoclax peak exposures were achieved at 5 to 8 hours under low-fat conditions, and the mean terminal-phase elimination half-life ranged between 14.1 and 18.2 hours at different doses. Venetoclax steady-state exposures showed minimal accumulation and increased proportionally over the dose range of 300 to 900 mg. Low-fat and high-fat meals increased venetoclax exposures by approximately 4-fold relative to the fasting state. Moderate CYP3A inhibitors increased venetoclax exposures by 40% to 60%, whereas weak CYP3A inhibitors had no effect. A negligible amount of venetoclax was excreted in the urine. In summary, venetoclax exhibits a pharmacokinetic profile that is compatible with once-daily dosing with food regardless of fat content. Concomitant use of venetoclax with moderate CYP3A inhibitors should be avoided or venetoclax dose should be reduced during the venetoclax initiation and ramp-up phase in CLL patients. Renal excretion plays a minimal role in the elimination of venetoclax. © 2016, The American College of Clinical Pharmacology.

A multicenter study of plasma use in the United States.

PubMed

Triulzi, Darrell; Gottschall, Jerome; Murphy, Edward; Wu, Yanyun; Ness, Paul; Kor, Daryl; Roubinian, Nareg; Fleischmann, Debra; Chowdhury, Dhuly; Brambilla, Donald

2015-06-01

Detailed information regarding plasma use in the United States is needed to identify opportunities for practice improvement and design of clinical trials of plasma therapy. Ten US hospitals collected detailed medical information from the electronic health records for 1 year (2010-2011) for all adult patients transfused with plasma. A total of 72,167 units of plasma were transfused in 19,596 doses to 9269 patients. The median dose of plasma was 2 units (interquartile range, 2-4; range 1-72); 15% of doses were 1 unit, and 45% were 2 units. When adjusted by patient body weight (kg), the median dose was 7.3 mL/kg (interquartile range, 5.5-12.0). The median pretransfusion international normalized ratio (INR) was 1.9 (25%-75% interquartile range, 1.6-2.6). A total of 22.5% of plasma transfusions were given to patients with an INR of less than 1.6 and 48.5% for an INR of 2.0 or more. The median posttransfusion INR was 1.6 (interquartile range, 1.4-2.0). Only 42% of plasma transfusions resulted in a posttransfusion INR of less than 1.6. Correction of INR increased as the plasma dose increased from 1 to 4 units (p < 0.001). There was no difference in the INR response to different types of plasma. The most common issue locations were general ward (38%) and intensive care unit (ICU; 42%). This large database describing plasma utilization in the United States provides evidence for both inadequate dosing and unnecessary transfusion. Measures to improve plasma transfusion practice and clinical trials should be directed at patients on medical and surgical wards and in the ICU where plasma is most commonly used. © 2014 AABB.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Battum, LJ van; Heukelom, S

Purpose This study investigates the origin of lateral optical density (OD) variation for Gafchromic film (EBT and EBT2) scanned in transmission mode with Epson flatbed scanners (1680 Expression Pro and 10000XL). Effects investigated are: cross talk, optical path length and polarization. Methods Cross talk has been examined with triangular shaped light-transmission sheets with OD ranging from 0 to opaque. Optical path length has been studied with absorptive and reflective OD-filters (OD range 0.2 to 2.0). Dependency on light-polarization on the scanner read out has been investigated using linear polarizer sheets. All experiments have been performed at centre scanner position (normmore » point) and at several lateral scan positions, without and with (un)irradiated EBT-film. Dose values used ranged between 0.2 to 9 Gy, yielding an OD-range between 0.25 to 1.1. Results The lateral OD variation is dose dependent and increases up to 14% at most lateral position for dose up to 9 Gy. Cross talk effect contributes to 0.5% in clinical used OD ranges but equals 2% for extreme high dose gradients. Film induced optical path length will effect the lateral OD variation up to 3% at most lateral points. Light polarization is inherent present in these scanners due to multiple reflection on mirrors. In addition film induced polarization is the most important effect generating the observed lateral OD variation. Both Gafchromic film base and sensitive layer have polarizing capabilities; for the sensitive layer its influence is dose dependent. Conclusions Lateral OD variation origins from optical physics (i.e. polarization and reflection) related to scanner and film construction. Cross talk can be ignored in film dosimetry for clinical used dose values and gradients. Therefore it is recommended to determine the lateral OD variation per film type and scanner.« less

A multicenter study of plasma use in the United States

PubMed Central

Triulzi, Darrell; Gottschall, Jerome; Murphy, Edward; Wu, Yanyun; Ness, Paul; Kor, Daryl; Roubinian, Nareg; Fleischmann, Debra; Chowdhury, Dhuly; Brambilla, Donald

2016-01-01

Background Detailed information regarding plasma use in the United States is needed to identify opportunities for practice improvement and design of clinical trials of plasma therapy. Study Design and Methods Ten US hospitals collected detailed medical information from the electronic health records for 1 year (2010-2011) for all adult patients transfused with plasma. Results A total of 72,167 units of plasma were transfused in 19,596 doses to 9269 patients. The median dose of plasma was 2 units (interquartile range, 2-4; range 1-72); 15% of doses were 1 unit, and 45% were 2 units. When adjusted by patient body weight (kg), the median dose was 7.3 mL/kg (interquartile range, 5.5-12.0). The median pretransfusion international normalized ratio (INR) was 1.9 (25%-75% interquartile range, 1.6-2.6). A total of 22.5% of plasma transfusions were given to patients with an INR of less than 1.6 and 48.5% for an INR of 2.0 or more. The median posttransfusion INR was 1.6 (interquartile range, 1.4-2.0). Only 42% of plasma transfusions resulted in a posttransfusion INR of less than 1.6. Correction of INR increased as the plasma dose increased from 1 to 4 units (p < 0.001). There was no difference in the INR response to different types of plasma. The most common issue locations were general ward (38%) and intensive care unit (ICU; 42%). Conclusion This large database describing plasma utilization in the United States provides evidence for both inadequate dosing and unnecessary transfusion. Measures to improve plasma transfusion practice and clinical trials should be directed at patients on medical and surgical wards and in the ICU where plasma is most commonly used. PMID:25522888

Comparison of doses to the rectum derived from treatment planning system with in-vivo dose values in vaginal vault brachytherapy using cylinder applicators

PubMed Central

Obed, Rachel Ibhade; Akinlade, Bidemi Idayat; Ntekim, Atara

2015-01-01

Purpose In-vivo measurements to determine doses to organs-at-risk can be an essential part of brachytherapy quality assurance (QA). This study compares calculated doses to the rectum with measured dose values as a means of QA in vaginal vault brachytherapy using cylinder applicators. Material and methods At the Department of Radiotherapy, University College Hospital (UCH), Ibadan, Nigeria, intracavitary brachytherapy (ICBT) was delivered by a GyneSource high-dose-rate (HDR) unit with 60Co. Standard 2D treatment plans were created with HDR basic 2.6 software for prescription doses 5-7 Gy at points 5 mm away from the posterior surface of vaginal cylinder applicators (20, 25, and 30 mm diameters). The LiF:Mg, Ti thermoluminescent dosimeter rods (1 x 6 mm) were irradiated to a dose of 7 Gy on Theratron 60Co machine for calibration purpose prior to clinical use. Measurements in each of 34 insertions involving fourteen patients were performed with 5 TLD-100 rods placed along a re-usable rectal marker positioned in the rectum. The dosimeters were read in Harshaw 3500 TLD reader and compared with doses derived from the treatment planning system (TPS) at 1 cm away from the dose prescription points. Results The mean calculated and measured doses ranged from 2.1-3.8 Gy and 1.2-5.6 Gy with averages of 3.0 ± 0.5 Gy and 3.1 ± 1.1 Gy, respectively, for treatment lengths 2-8 cm along the cylinder-applicators. The mean values correspond to 48.9% and 50.8% of the prescribed doses, respectively. The deviations of the mean in-vivo doses from the TPS values ranged from –1.9 to 2.1 Gy with a p-value of 0.427. Conclusions This study was part of efforts to verify rectal dose obtained from the TPS during vaginal vault brachytherapy. There was no significant difference in the dose to the rectum from the two methods of measurements. PMID:26816506

Efficacy and Safety of OnabotulinumtoxinA Treatment of Forehead Lines: A Multicenter, Randomized, Dose-Ranging Controlled Trial.

PubMed

Solish, Nowell; Rivers, Jason K; Humphrey, Shannon; Muhn, Channy; Somogyi, Chris; Lei, Xiaofang; Bhogal, Meetu; Caulkins, Carrie

2016-03-01

Various onabotulinumtoxinA doses are effective in treating forehead lines (FHL), with a trend toward lower doses. To evaluate efficacy and safety of onabotulinumtoxinA dose-ranging treatment of FHL when the frontalis area and glabellar complex are treated together. Adults with moderate-to-severe FHL received onabotulinumtoxinA 40 U (FHL, 20 U; glabellar lines [GL], 20 U), 30 U (FHL, 10 U; GL, 20 U), or placebo. Response was assessed at weeks 1, 2, day 30, and monthly to day 180. Coprimary efficacy end points were investigator- and subject-assessed Facial Wrinkle Scale scores of none or mild (day 30). Patient-reported outcomes, onset/duration of effect, and adverse events (AEs) were evaluated. Responder rates (investigator/subject, respectively) were 40-U group, 91.2%/89.5%; 30-U group, 86.4%/81.4%; placebo, 1.7%/5.1%. OnabotulinumtoxinA resulted in significantly greater responder rates than placebo (p < .001). Adverse events were mild to moderate and similar between groups (most common AEs: nasopharyngitis [4.6%] and headache [4.0%]). Treatment of FHL with onabotulinumtoxinA 40 and 30 U (in frontalis and glabellar complex muscles) was tolerable, effective, and sustained. Both doses significantly reduced FHL severity; however, the 40-U dose demonstrated a trend toward greater sustained benefit and longer duration of effect versus the 30-U dose, with similar AE rates.

Uranium-238 and thorium-232 series concentrations in soil, radon-222 indoor and drinking water concentrations and dose assessment in the city of Aldama, Chihuahua, Mexico.

PubMed

Colmenero Sujo, L; Montero Cabrera, M E; Villalba, L; Rentería Villalobos, M; Torres Moye, E; García León, M; García-Tenorio, R; Mireles García, F; Herrera Peraza, E F; Sánchez Aroche, D

2004-01-01

High-resolution gamma spectrometry was used to determine the concentration of 40K, 238U and 232Th series in soil samples taken from areas surrounding the city of Aldama, in Chihuahua. Results of indoor air short-time sampling, with diffusion barrier charcoal detectors, revealed relatively high indoor radon levels, ranging from 29 to 422 Bq/m3; the radon concentrations detected exceeded 148 Bq/m3 in 76% of the homes tested. Additionally, liquid scintillation counting showed concentrations of radon in drinking water ranging from 4.3 to 42 kBq/m3. The high activity of 238U in soil found in some places may be a result of the uranium milling process performed 20 years ago in the area. High radon concentrations indoor and in water may be explained by assuming the presence of uranium-bearing rocks underneath of the city, similar to a felsic dike located near Aldama. The estimated annual effective dose of gamma radiation from the soil and radon inhalation was 3.83 mSv.

Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments.

PubMed

Agarwal, Suresh K; DiNardo, Courtney D; Potluri, Jalaja; Dunbar, Martin; Kantarjian, Hagop M; Humerickhouse, Rod A; Wong, Shekman L; Menon, Rajeev M; Konopleva, Marina Y; Salem, Ahmed Hamed

2017-02-01

The effect of posaconazole, a strong cytochrome P450 3A (CYP3A) inhibitor and commonly used antifungal agent, on the pharmacokinetic properties of venetoclax, a CYP3A substrate, was evaluated in patients with acute myeloid leukemia to determine the dose adjustments needed to manage this potential interaction. Twelve patients received 20- to 200-mg ramp-up treatment with oral venetoclax and 20 mg/m 2 of intravenous decitabine on days 1 through 5, followed by 400 mg of venetoclax alone on days 6 through 20. On days 21 through 28, patients received 300 mg of posaconazole plus reduced doses of venetoclax (50 or 100 mg) to account for expected increases in venetoclax plasma concentrations. Blood samples were collected before dosing and up to 24 hours after the venetoclax dose on days 20 and 28. Compared with a venetoclax dose of 400 mg when administered alone (day 20), coadministration of venetoclax at a 50-mg dose with multiple doses of posaconazole increased mean venetoclax C max and AUC 0-24 by 53% and 76%, respectively, whereas coadministration of venetoclax at a 100-mg dose with posaconazole increased mean venetoclax C max and AUC 0-24 by 93% and 155%, respectively. When adjusted for different doses and nonlinearity, posaconazole was estimated to increase venetoclax C max and AUC 0-24 by 7.1- and 8.8-fold, respectively. Both the 50- and 100-mg venetoclax doses administered with posaconazole were well tolerated. The results are consistent with inhibition of CYP3A-mediated metabolism of venetoclax. Posaconazole can be used for antifungal prophylaxis in patients with acute myeloid leukemia receiving venetoclax after reducing the venetoclax dose by at least 75%. ClinicalTrials.gov identifier: NCT02203773. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Degradation of the Bragg peak due to inhomogeneities.

PubMed

Urie, M; Goitein, M; Holley, W R; Chen, G T

1986-01-01

The rapid fall-off of dose at the end of range of heavy charged particle beams has the potential in therapeutic applications of sparing critical structures just distal to the target volume. Here we explored the effects of highly inhomogeneous regions on this desirable depth-dose characteristic. The proton depth-dose distribution behind a lucite-air interface parallel to the beam was bimodal, indicating the presence of two groups of protons with different residual ranges, creating a step-like depth-dose distribution at the end of range. The residual ranges became more spread out as the interface was angled at 3 degrees, and still more at 6 degrees, to the direction of the beam. A second experiment showed little significant effect on the distal depth-dose of protons having passed through a mosaic of teflon and lucite. Anatomic studies demonstrated significant effects of complex fine inhomogeneities on the end of range characteristics. Monoenergetic protons passing through the petrous ridges and mastoid air cells in the base of skull showed a dramatic degradation of the distal Bragg peak. In beams with spread out Bragg peaks passing through regions of the base of skull, the distal fall-off from 90 to 20% dose was increased from its nominal 6 to well over 32 mm. Heavy ions showed a corresponding degradation in their ends of range. In the worst case in the base of skull region, a monoenergetic neon beam showed a broadening of the full width at half maximum of the Bragg peak to over 15 mm (compared with 4 mm in a homogeneous unit density medium). A similar effect was found with carbon ions in the abdomen, where the full width at half maximum of the Bragg peak (nominally 5.5 mm) was found to be greater than 25 mm behind gas-soft-tissue interfaces. We address the implications of these data for dose computation with heavy charged particles.

Hearing Outcomes After Stereotactic Radiosurgery for Unilateral Intracanalicular Vestibular Schwannomas: Implication of Transient Volume Expansion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Young-Hoon; Department of Neurosurgery, Seoul National University College of Medicine, Seoul; Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.kr

2013-01-01

Purpose: We evaluated the prognostic factors for hearing outcomes after stereotactic radiosurgery (SRS) for unilateral sporadic intracanalicular vestibular schwannomas (IC-VSs) as a clinical homogeneous group of VSs. Methods and Materials: Sixty consecutive patients with unilateral sporadic IC-VSs, defined as tumors in the internal acoustic canal, and serviceable hearing (Gardner-Roberson grade 1 or 2) were treated with SRS as an initial treatment. The mean tumor volume was 0.34 {+-} 0.03 cm{sup 3} (range, 0.03-1.00 cm{sup 3}), and the mean marginal dose was 12.2 {+-} 0.1 Gy (range, 11.5-13.0 Gy). The median follow-up duration was 62 months (range, 36-141 months). Results: Themore » actuarial rates of serviceable hearing preservation were 70%, 63%, and 55% at 1, 2, and 5 years after SRS, respectively. In multivariate analysis, transient volume expansion of {>=}20% from initial tumor size was a statistically significant risk factor for loss of serviceable hearing and hearing deterioration (increase of pure tone average {>=}20 dB) (odds ratio = 7.638; 95% confidence interval, 2.317-25.181; P=.001 and odds ratio = 3.507; 95% confidence interval, 1.228-10.018; P=.019, respectively). The cochlear radiation dose did not reach statistical significance. Conclusions: Transient volume expansion after SRS for VSs seems to be correlated with hearing deterioration when defined properly in a clinically homogeneous group of patients.« less

Dose to the Developing Dentition During Therapeutic Irradiation: Organ at Risk Determination and Clinical Implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, Reid F., E-mail: Reid.Thompson@uphs.upenn.edu; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania; Schneider, Ralf A., E-mail: ralf.schneider@psi.ch

Purpose: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. Methods and Materials: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions formore » a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. Results: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. Conclusions: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the largest doses of radiation at the youngest ages; however, multiple factors including concurrent chemotherapy confounded the dose-effect relationship. Further studies with larger cohorts and appropriate controls will be required.« less

SU-F-T-626: Intracranial SRS Re-Treatment Without Acquisition of New CT Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiant, D; Manning, M; Liu, H

Purpose: Linear accelerator based stereotactic radiosurgery (SRS) for multiple intracranial lesions with frequent surveillance is becoming a popular treatment option. This strategy leads to retreatment with SRS as new lesions arise. Currently, each course of treatment uses magnetic resonance (MR) and computed tomography (CT) images for treatment planning. We propose that new MR images, with course 1 CT images, may be used for future treatment plans with negligible loss of dosimetric accuracy. Methods: Ten patients that received multiple courses of SRS were retrospectively reviewed. The treatment plans and contours from non-initial courses were copied to the initial CTs and recalculated.more » Doses metrics for the plans calculated on the initial CTs and later CTs were compared. All CT scans were acquired on a Philips CT scanner with a 600 mm field of view and 1 mm slice thickness (Philips Healthcare, Andover, MA). All targets were planned to 20 Gy and calculated in Eclipse V. 13.6 (Varian, Palo Alto, CA) using analytic anisotropic algorithm with 1 mm calculation grid. Results: Sixteen lesions were evaluated. The mean time between courses was 250 +/− 215 days (range 103–979). The mean target volume was 2.0 +/− 2.9 cc (range 0.1–10.1). The average difference in mean target dose between the two calculations was 0.2 +/− 0.3 Gy (range 0.0 – 1.0). The mean conformity index (CI) was 1.28 +/− 0.14 (range 1.07 – 1.82). The average difference in CI was 0.03 +/− 0.16 (range 0.00 – 0.44). Targets volumes < 0.5 cc showed the largest changes in both metrics. Conclusion: Continued treatment based on initial CT images is feasible. Dose calculation on the initial CT for future treatments provides reasonable dosimetric accuracy. Changes in dose metrics are largest for small volumes, and are likely dominated by partial volume effects in target definition.« less

TH-A-9A-10: Prostate SBRT Delivery with Flattening-Filter-Free Mode: Benefit and Accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, T; Yuan, L; Sheng, Y

Purpose: Flattening-filter-free (FFF) beam mode offered on TrueBeam™ linac enables delivering IMRT at 2400 MU/min dose rate. This study investigates the benefit and delivery accuracy of using high dose rate in the context of prostate SBRT. Methods: 8 prostate SBRT patients were retrospectively studied. In 5 cases treated with 600-MU/min dose rate, continuous prostate motion data acquired during radiation-beam-on was used to analyze motion range. In addition, the initial 1/3 of prostate motion trajectories during each radiation-beam-on was separated to simulate motion range if 2400-MU/min were used. To analyze delivery accuracy in FFF mode, MLC trajectory log files from anmore » additional 3 cases treated at 2400-MU/min were acquired. These log files record MLC expected and actual positions every 20ms, and therefore can be used to reveal delivery accuracy. Results: (1) Benefit. On average treatment at 600-MU/min takes 30s per beam; whereas 2400-MU/min requires only 11s. When shortening delivery time to ~1/3, the prostate motion range was significantly smaller (p<0.001). Largest motion reduction occurred in Sup-Inf direction, from [−3.3mm, 2.1mm] to [−1.7mm, 1.7mm], followed by reduction from [−2.1mm, 2.4mm] to [−1.0mm, 2.4mm] in Ant-Pos direction. No change observed in LR direction [−0.8mm, 0.6mm]. The combined motion amplitude (vector norm) confirms that average motion and ranges are significantly smaller when beam-on was limited to the 1st 1/3 of actual delivery time. (2) Accuracy. Trajectory log file analysis showed excellent delivery accuracy with at 2400 MU/min. Most leaf deviations during beam-on were within 0.07mm (99-percentile). Maximum leaf-opening deviations during each beam-on were all under 0.1mm for all leaves. Dose-rate was maintained at 2400-MU/min during beam-on without dipping. Conclusion: Delivery prostate SBRT with 2400 MU/min is both beneficial and accurate. High dose rates significantly reduced both treatment time and intra-beam prostate motion range. Excellent delivery accuracy was confirmed with very small leaf motion deviation.« less

Risk factors for scoliosis in children with neuroblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paulino, Arnold C.; Fowler, B. Zach

2005-03-01

Purpose: To determine the risk factors for scoliosis in children treated for neuroblastoma. Methods and materials: From 1957 to 1997, 58 children with neuroblastoma were treated at one institution and have survived a minimum of 5 years. There were 35 boys and 23 girls with a median age of 6 months (range, 2 weeks to 15 years) at initial diagnosis. Primary site was located in the adrenal gland in 25 (43.1%), abdominal/nonadrenal in 16 (27.6%), thoracic in 12 (20.7%), cervical in 3 (5.3%), and pelvic region in 2 (3.5%). The International Neuroblastoma Staging System (INSS) stage was Stage 1 inmore » 10 (17.2%), Stage 2A in 7 (12.1%), Stage 2B in 5 (8.6%), Stage 3 in 22 (37.9%), Stage 4 in 4 (6.9%), and Stage 4S in 10 (17.2%). Thirty-three (56.9%) received chemotherapy whereas 5 (8.6%) had a laminectomy as part of the surgical procedure. Twenty-seven (46.6%) received radiotherapy (RT). Beam energy was 1.25 MV in 11 (41%), 250 kV in 10 (37%), 4 MV in 4 (15%), and 6-MV photons in 1 patient. One patient received 300 cGy in 1 fraction total skin RT using 6-MeV electrons. For the remaining patients, fraction size was 100 cGy in 6 (22%), 150-180 cGy in 11 (41%), 200 cGy in 4 (15%), and 250-300 cGy in 3. Three patients had total body irradiation at 333 cGy for 3 fractions. For all children who received RT, median total dose was 2000 cGy (range, 300-3900 cGy). Patients who were treated with RT had plain films of the irradiated area every 1 to 2 years until at least the age of puberty. Median follow-up was 10 years (range, 5-46 years). Results: The overall 5-, 10-, and 15-year scoliosis-free rates were 87.6%, 79.0%, and 76.0% respectively. Twelve (21%) developed scoliosis at a median time of 51 months (range, 8-137 months). The degree of scoliosis was mild ({<=}20 deg ) in 8 (67%). Four had scoliosis ranging from 30 deg to 66 deg ; 3 of these patients required surgical intervention, whereas 1 had an underlying Duchenne muscular dystrophy which manifested itself 8 years after diagnosis of neuroblastoma. Median time to scoliosis was 23 months (range, 8-54 months) in children who had a laminectomy. On multivariate analysis, both history of laminectomy (p = 0.0005) and use of RT (p = 0.0284) were found to be risk factors for development of scoliosis. Gender, age at diagnosis, INSS stage, primary site, and use of chemotherapy were not found to be significant. Both RT fraction size and beam energy were also not significant, but increasing total RT dose was found to be significant (p = 0.0039). The 15-year scoliosis-free rates were 20% for children who had a laminectomy and 81.3% for those who did not have a laminectomy. The 15-year scoliosis-free rates for children treated with RT doses 0 cGy, 1-1750 cGy, 1751-2300 cGy, and >2300 cGy were 91.7%, 87.5%, 51.4%, and 44.4% respectively. Conclusions: Treatment-related factors, namely laminectomy and radiotherapy, were found to increase the risk of scoliosis in patients with neuroblastoma. Children who had a laminectomy were more likely to manifest scoliosis earlier. Increasing RT dose was found to impact adversely on the development of scoliosis.« less

Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study.

PubMed

Attanasio, Roberto; Epaminonda, Paolo; Motti, Enrico; Giugni, Enrico; Ventrella, Laura; Cozzi, Renato; Farabola, Mario; Loli, Paola; Beck-Peccoz, Paolo; Arosio, Maura

2003-07-01

Stereotactic radiosurgery by gamma-knife (GK) is an attractive therapeutic option after failure of microsurgical removal in patients with pituitary adenoma. In these tumors or remnants of them, it aims to obtain the arrest of cell proliferation and hormone hypersecretion using a single precise high dose of ionizing radiation, sparing surrounding structures. The long-term efficacy and toxicity of GK in acromegaly are only partially known. Thirty acromegalic patients (14 women and 16 men) entered a prospective study of GK treatment. Most were surgical failures, whereas in 3 GK was the primary treatment. Imaging of the adenoma and target coordinates identification were obtained by high resolution magnetic resonance imaging. All patients were treated with multiple isocenters (mean, 8; range, 3-11). The 50% isodose was used in 27 patients (90%). The mean margin dose was 20 Gy (range, 15-35), and the dose to the visual pathways was always less than 8 Gy. After a median follow-up of 46 months (range, 9-96), IGF-I fell from 805 micro g/liter (median; interquartile range, 640-994) to 460 micro g/liter (interquartile range, 217-654; P = 0.0002), and normal age-matched IGF-I levels were reached in 7 patients (23%). Mean GH levels decreased from 10 micro g/liter (interquartile range, 6.4-15) to 2.9 micro g/liter (interquartile range, 2-5.3; P < 0.0001), reaching levels below 2.5 micro g/liter in 11 (37%). The rate of persistently pathological hormonal levels was still 70% at 5 yr by Kaplan-Meier analysis. The median volume was 1.43 ml (range, 0.20-3.7). Tumor shrinkage (at least 25% of basal volume) occurred after 24 months (range, 12-36) in 11 of 19 patients (58% of assessable patients). The rate of shrinkage was 79% at 4 yr. In no case was further growth observed. Only 1 patient complained of side-effects (severe headache and nausea immediately after the procedure, with full recovery in a few days with steroid therapy). Anterior pituitary failures were observed in 2 patients, who already had partial hypopituitarism, after 2 and 6 yr, respectively. No patient developed visual deficits. GK is a valid adjunctive tool in the management of acromegaly that controls GH/IGF-I hypersecretion and tumor growth, with shrinkage of adenoma and no recurrence of the disease in the considered observation period and with low acute and chronic toxicity.

Gentamicin ototoxicity: a 23-year selected case series of 103 patients.

PubMed

Ahmed, Rebekah M; Hannigan, Imelda P; MacDougall, Hamish G; Chan, Raymond C; Halmagyi, G Michael

2012-06-18

To review patients with severe bilateral vestibular loss associated with gentamicin treatment in hospital. A retrospective case series of presentations to a balance disorders clinic between 1988 and 2010. Relationship between vestibulotoxicity and gentamicin dose or dosing profile; indications for prescribing gentamicin. 103 patients (age, 18-84 years; mean, 64 years) presented with imbalance, oscillopsia or both, but none had vertigo. Only three noted some hearing impairment after having gentamicin, but audiometric thresholds for all patients were consistent with their age. In all patients, the following tests gave positive results: a bilateral clinical head-impulse test, a vertical head-shaking test for vertical oscillopsia, and a foam Romberg test. In 21 patients, imbalance occurred during gentamicin treatment (ignored or dismissed by prescribers in 20) and in 66 after treatment; the remaining 16 could not recall when symptoms were first noticed, except that it was after gentamicin treatment in hospital. Total gentamicin dose range was 2-318 mg/kg (mean, 52 mg/kg), daily dose range was 1.5-5.6 mg/kg (mean, 3.5mg/kg), and duration was 1-80 days (mean, 17 days). Six patients had only a single dose; 26 had five or fewer doses. Serum gentamicin levels, measured in 82 patients, were in the recommended range in 59. Time to diagnosis ranged from 4 days to 15 years. Nephrotoxicity developed in 43 patients. Gentamicin dosage complied with contemporary or current Australian antibiotic guidelines in under half the patients. Gentamicin ototoxicity is vestibular, not cochlear, producing permanent loss of balance, but not of hearing. Gentamicin can be vestibulotoxic in any dose, in any regimen, at any serum level.

Feasibility of intensity-modulated radiotherapy for esophageal cancer in definite chemoradiotherapy.

PubMed

Hsieh, He-Yuan; Yeh, Hui-Ling; Hsu, Chung-Ping; Lin, Jin-Ching; Chuang, Cheng-Yen; Lin, Jai-Fu; Chang, Chen-Fa

2016-07-01

Esophageal cancer is a highly lethal malignancy, and its treatment has undergone a major evolution over the past 15 years. The objective of this study was to report our experience on the efficacy of definite chemoradiotherapy with the intensity-modulated radiotherapy (IMRT) technique in treating locally advanced esophageal cancer. From September 2004 to November 2011, 39 patients with biopsy-proven esophageal cancer, clinical stage T1-4N0-3M0 according to the American Joint Committee on Cancer 7(th) edition were enrolled. In these enrolled cases, either the tumor was unresectable or the patients refused surgery. All patients received a total radiation dose of 40-56 Gy in 20-28 fractions using IMRT planning. Five to seven radiation beam angles were designed according to the specific shape of the clinical target volume (CTV) and were delivered by a linear accelerator with photons of 6-10 MV energy. The gross tumor volume, CTV, planning target volume, and the organs at risk were outlined, and the homogeneity index (HI) and the conformity index (CI) were calculated. The treatment-related toxicities were also reviewed. The mean follow-up time was 22.4 months (range, 2.0-91.0 months). The 2- and 3-year overall survival rates were 30% and 28%, respectively. The most common Grade 3/4 toxicity was hematologic toxicity (43.6%). The IMRT plans showed high-dose homogeneity to the target, with a calculated HI of 0.9. The calculated CI of 0.8 also showed high conformity treatment dose to target within an acceptable dose range. For the total lungs, the average mean dose was 1313.7 cGy. The V5 and V20 of the total lungs were 67.8% and 23.4%, respectively. For the heart, the average mean dose was 2319.2 cGy. The V30 and V35 of the heart were 30.2% and 21.5%, respectively. Concurrent chemoradiotherapy using the IMRT technique for treating locally advanced unresectable esophageal cancer is feasible, with better conformity of target volume as well as improved sparing of organs at risk. Copyright © 2016. Published by Elsevier Taiwan LLC.

Hypofractionated stereotactic radiotherapy combined with topotecan in recurrent malignant glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wurm, Reinhard E.; Kuczer, David A.; Schlenger, Lorenz

Purpose: To assess hypofractionated stereotactic radiotherapy (H-SRT) with concurrent topotecan in patients with recurrent malignant glioma. Methods and Materials: Between February 1998 and December 2001, 25 patients with recurrent malignant glioma were treated in a phase I-II study (8 females and 17 males; median age, 45 years; range, 11-66 years; median Karnofsky performance status, 80%, range, 50-100%; median Mini Mental Standard Examination score, 25 points; range, 10-30 points). Of the 25 patients, 20% had World Health Organization Grade III and 80% World Health Organization Grade IV glioma. All patients had been treated previously by external beam radiotherapy with 54.4 Gymore » in 34 fractions twice daily, at least 6 h apart, within 3.5 weeks or 60 Gy in 30 fractions within 6 weeks. In addition, 84% had already received at least one chemotherapy regimen for recurrence. The median H-SRT dose at the 80% isodose was 25 Gy, and the maximal dose was 30 Gy delivered in five to six fractions on consecutive days. Topotecan (1.1 mg/m{sup 2}/d) was given as a continuous i.v. infusion during H-SRT. Depending on the toxicity and compliance, patients received an additional 48 topotecan courses. Results: For all patients, the actuarial median progression-free survival was 10.5 months (range, 1.4-47.8 months), the median functional survival was 12.6 months (range, 1.6-49.5 months), and the median overall survival was 14.5 months (range, 3-56.4 months). Twelve percent of patients developed presumed adverse radiation effects (Radiation Therapy Oncology Group Grade 2). According to the Common Toxicity Criteria, version 2.0, no topotecan-related Grade 4 toxicity was noted. Grade 3 neutropenia was documented after 14 and Grade 3 thrombopenia after 12 courses. Conclusion: H-SRT with topotecan is feasible and well-tolerated in patients with recurrent high-grade glioma and results in similar survival compared with other repeat treatment modalities.« less

Dosimetric evaluation of a new OneDose MOSFET for Ir-192 energy.

PubMed

Kinhikar, Rajesh A; Sharma, Pramod K; Tambe, Chandrashekhar M; Deshpande, Deepak D

2006-03-07

The purpose of this study was to investigate dosimetry (reproducibility, energy correction, relative response with distance from source, linearity with threshold dose, rate of fading, temperature and angular dependence) of a newly designed OneDosetrade mark MOSFET patient dosimetry system for use in HDR brachytherapy with Ir-192 energy. All measurements were performed with a MicroSelectron HDR unit and OneDose MOSFET detectors. All dosimeters were normalized to 3 min post-irradiation to minimize fading effects. All dosimeters gave reproducible readings with mean deviation of 1.8% (SD 0.4) and 2.4% (SD 0.6) for 0 degrees and 180 degrees incidences, respectively. The mean energy correction factor was found to be 1.1 (range 1.06-1.12). Overall, there was 60% and 40% mean response of the MOSFET at 2 and 3 cm, respectively, from the source. MOSFET results showed good agreement with TLD and parallel plate ion chamber. Linear dose response with threshold voltage shift was observed with applied doses of 0.3 Gy-5 Gy with Ir-192 energy. Linearity (R2 = 1) was observed in the MOSFET signal with the applied dose range of 0.3 Gy-5 Gy with Ir-192 energy. Fading effects were less than 1% after 10 min and the MOSFET detectors stayed stable (within 5%) over a period of 1 month. The MOSFET response was found to be decreased by approximately 1.5% at 37 degrees C compared to 20 degrees C. The isotropic response of the MOSFET was found to be within +/-6%. A maximum deviation of 5.5% was obtained between 0 degrees and 180 degrees for both the axes and this should be considered in clinical applications. The small size, cable-less, instant readout, permanent storage of dose and ease of use make the MOSFET a novel dosimeter and beneficial to patients for skin dose measurements with HDRBT using an Ir-192 source compared to the labour demanding and time-consuming TLDs.

TLD postal dose intercomparison for megavoltage units in Poland.

PubMed

Izewska, J; Gajewski, R; Gwiazdowska, B; Kania, M; Rostkowska, J

1995-08-01

The aim of the TLD pilot study was to investigate and to reduce the uncertainties involved in the measurements of absorbed dose and to improve the consistency in dose determination in the regional radiotherapy centres in Poland. The intercomparison was organized by the SSDL. It covered absorbed dose measurements under reference conditions for Co-60, high energy X-rays and electron beams. LiF powder type MT-N was used for the irradiations and read with the Harshaw TLD reader model 2000B/2000C. The TLD system was set up and an analysis of the factors influencing the accuracy of absorbed dose measurements with TL-detectors was performed to evaluate and minimize the measurement uncertainty. A fading not exceeding 2% in 12 weeks was found. The relative energy correction factor did not exceed 3% for X-rays in the range 4-15 MV, and 4% for electron beams between 6 and 20 MeV. A total of 34 beams was checked. Deviation of +/- 3.5% stated and evaluated dose was considered acceptable for photons and +/- 5% for electron beams. The results for Co-60, high energy X-rays and electron beams showed that there were two, three and no centres, respectively, beyond acceptance levels. The sources of errors for all deviations out of this range were thoroughly investigated, discussed and corrected, however two deviations remained unexplained. The pilot study resulted in an improvement of the accuracy and consistency of dosimetry in Poland.

Effect of freezing, irradiation, and frozen storage on survival of Salmonella in concentrated orange juice.

PubMed

Niemira, Brendan A; Sommers, Christopher H; Boyd, Glenn

2003-10-01

Six strains of Salmonella (Anatum F4317, Dublin 15480, Enteritidis 13076, Enteritidis WY15159, Stanley H0588, and Typhimurium 14028) were individually inoculated into orange juice concentrate (OJC) and frozen to -20 degrees C. The frozen samples were treated with 0 (nonirradiated), 0.5, 1.0, or 2.0 kGy of gamma radiation and held frozen for 1 h, and the surviving bacterial population was assessed. The strains showed significant variability in their response to freezing and to freezing in combination with irradiation. The response was dose dependent. Relative to the nonfrozen, nonirradiated control, the reduction following the highest dose (2.0 kGy) ranged from 1.29 log CFU/ml (Salmonella Typhimurium) to 2.17 log CFU/ml (Salmonella Stanley). Samples of OJC inoculated with Salmonella Enteritidis WY15159 and irradiated were stored at -20 degrees C for 1, 2, 7, or 14 days, and the surviving population was determined. Relative to the nonfrozen, nonirradiated control, after 14 days, the population was reduced by 1.2 log CFU/ml in the nonirradiated samples and by 3.3 log CFU/ml following treatment with 2.0 kGy. The combination of frozen storage plus irradiation resulted in greater overall reductions than either process alone.

Dose-volumetric parameters of acute esophageal toxicity in patients with lung cancer treated with three-dimensional conformal radiotherapy.

PubMed

Kim, Tae Hyun; Cho, Kwan Ho; Pyo, Hong Ryull; Lee, Jin Soo; Han, Ji Youn; Zo, Jae Ill; Lee, Jong Mog; Hong, Eun Kyoung; Choi, Il Ju; Park, Sung Yong; Shin, Kyung Hwan; Kim, Dae Yong; Kim, Joo Young

2005-07-15

To retrospectively evaluate which dose-volumetric parameters are associated with the risk of > or = Grade 3 acute esophageal toxicity (AET) in lung cancer patients treated with three-dimensional conformal radiotherapy (3D-CRT). One hundred twenty-four lung cancer patients treated curatively with 3D-CRT were retrospectively analyzed. All patients received conventionally fractionated radiotherapy (RT) with median dose of 60 Gy (range, 54-66 Gy) delivered in 30 fractions (range, 27-33 fractions). Thirty-one patients underwent curative surgery before RT. Ninety-two patients received chemotherapy (induction, 18; concurrent +/- induction, 74). Acute esophageal toxicity was scored by Radiation Therapy Oncology Group criteria. The parameters analyzed included sex; age; Karnofsky performance score; weight loss; surgery; concurrent chemotherapy; the percentages of organ volume receiving > or =20 Gy (V20), > or =30 Gy (V30), > or =40 Gy (V40), > or =50 Gy (V50), > or =55 Gy (V55), > or = 58 Gy (V58), > or =60 Gy (V60), and > or =63 Gy (V63); the percent and absolute length of the esophagus irradiated; the maximum and mean dose to the esophagus; and normal tissue complication probability. Of the 124 patients, 15 patients (12.1%) had Grade 3 AET, and 1 (0.8%) patient had Grade 4 AET. There was no fatal Grade 5 AET. In univariate and multivariate logistic regression analyses, concurrent chemotherapy and V60 were significantly associated with the development of severe (> or = Grade 3) AET (p < 0.05). Severe AET was observed in 15 of 74 patients (20.3%) who received concurrent chemotherapy, and in 1 of 50 patients (2.0%) who did not (p = 0.002). Severe AET was observed in 5 of 87 patients (5.7%) with V60 < or = 30% and in 11 of 37 patients (29.7%) with V60 > 30% (p < 0.001). Among 50 patients who did not receive concurrent chemotherapy, severe AET was observed in 0 of 43 patients (0%) with V60 < or = 30% and in 1 of 7 patients (14.2%) with V60 > 30% (p = 0.140). Among 74 patients who received concurrent chemotherapy, severe AET was observed in 5 of 44 patients (11.4%) with V60 < or = 30% and in 10 of 30 patients (33.3%) with V60 > 30% (p = 0.037). Concurrent chemotherapy and V60 were associated with the development of severe AET > or = Grade 3. For patients being treated with concurrent chemotherapy, V60 is considered to be a useful parameter predicting the risk of severe AET after conventionally fractionated 3D-CRT for lung cancer.

Dosimetric evaluation of the OneDoseTM MOSFET for measuring kilovoltage imaging dose from image-guided radiotherapy procedures.

PubMed

Ding, George X; Coffey, Charles W

2010-09-01

The purpose of this study is to investigate the feasibility of using a single-use dosimeter, OneDose MOSFET designed for in vivo patient dosimetry, for measuring the radiation dose from kilovoltage (kV) x rays resulting from image-guided procedures. The OneDose MOSFET dosimeters were precalibrated by the manufacturer using Co-60 beams. Their energy response and characteristics for kV x rays were investigated by using an ionization chamber, in which the air-kerma calibration factors were obtained from an Accredited Dosimetry Calibration Laboratory (ADCL). The dosimetric properties have been tested for typical kV beams used in image-guided radiation therapy (IGRT). The direct dose reading from the OneDose system needs to be multiplied by a correction factor ranging from 0.30 to 0.35 for kilovoltage x rays ranging from 50 to 125 kVp, respectively. In addition to energy response, the OneDose dosimeter has up to a 20% reduced sensitivity for beams (70-125 kVp) incident from the back of the OneDose detector. The uncertainty in measuring dose resulting from a kilovoltage beam used in IGRT is approximately 20%; this uncertainty is mainly due to the sensitivity dependence of the incident beam direction relative to the OneDose detector. The ease of use may allow the dosimeter to be suitable for estimating the dose resulting from image-guided procedures.

CT-Guided Transgluteal Biopsy for Systematic Random Sampling of the Prostate in Patients Without Rectal Access.

PubMed

Goenka, Ajit H; Remer, Erick M; Veniero, Joseph C; Thupili, Chakradhar R; Klein, Eric A

2015-09-01

The objective of our study was to review our experience with CT-guided transgluteal prostate biopsy in patients without rectal access. Twenty-one CT-guided transgluteal prostate biopsy procedures were performed in 16 men (mean age, 68 years; age range, 60-78 years) who were under conscious sedation. The mean prostate-specific antigen (PSA) value was 11.4 ng/mL (range, 2.3-39.4 ng/mL). Six had seven prior unsuccessful transperineal or transurethral biopsies. Biopsy results, complications, sedation time, and radiation dose were recorded. The mean PSA values and number of core specimens were compared between patients with malignant results and patients with nonmalignant results using the Student t test. The average procedural sedation time was 50.6 minutes (range, 15-90 minutes) (n = 20), and the mean effective radiation dose was 8.2 mSv (median, 6.6 mSv; range 3.6-19.3 mSv) (n = 13). Twenty of the 21 (95%) procedures were technically successful. The only complication was a single episode of gross hematuria and penile pain in one patient, which resolved spontaneously. Of 20 successful biopsies, 8 (40%) yielded adenocarcinoma (Gleason score: mean, 8; range, 7-9). Twelve biopsies yielded nonmalignant results (60%): high-grade prostatic intraepithelial neoplasia (n = 3) or benign prostatic tissue with or without inflammation (n = 9). Three patients had carcinoma diagnosed on subsequent biopsies (second biopsy, n = 2 patients; third biopsy, n = 1 patient). A malignant biopsy result was not significantly associated with the number of core specimens (p = 0.3) or the mean PSA value (p = 0.1). CT-guided transgluteal prostate biopsy is a safe and reliable technique for the systematic random sampling of the prostate in patients without a rectal access. In patients with initial negative biopsy results, repeat biopsy should be considered if there is a persistent rise in the PSA value.

Contribution of time-activity pattern and microenvironment to black carbon (BC) inhalation exposure and potential internal dose among elementary school children

NASA Astrophysics Data System (ADS)

Jeong, Hyeran; Park, Donguk

2017-09-01

The aims of this study were to quantify the contributions of activities or microenvironments (MEs) to daily total exposure to and potential dose of black carbon (BC). Daily BC exposures (24-h) were monitored using a micro-aethalometer micoAeth AE51 with forty school-aged children living in an urban area in Korea from August 2015 to January 2016. The children's time-activity patterns and the MEs they visited were investigated by means of a time-activity diary (TAD) and follow-up interviews with the children and their parents. Potential inhaled dose was estimated by multiplying the airborne BC concentrations (μg/m3) we monitored for the time the children spent in a particular ME by the inhalation rate (IR, m3/h) for the time-activity performed. The contribution of activities and MEs to overall daily exposure to and potential dose of BC was quantified. Overall mean daily potential dose was equal to 24.1 ± 10.6 μg/day (range: 6.6-46.3 μg/day). The largest contribution to BC exposure and potential dose (51.9% and 41.7% respectively) occurred in the home thanks to the large amount of time spent there. Transportation was where children received the most intense exposure to (14.8%) and potential dose (20.2%) of BC, while it accounted for 7.6% of daily time. School on weekdays during the semester was responsible for 20.3% of exposure and 22.5% of potential dose. Contribution to BC exposure and potential dose was altered by several time-activity parameters, such as type of day (weekdays vs. weekends; school days vs. holidays), season, and gender. Traveling by motor vehicle and subway showed more elevated exposure or potential dose intensity on weekdays or school days, probably influenced by the increased surrounding traffic volumes on these days compared to on weekends or holidays. This study may be used to prioritize targets for minimizing children's exposure to BC and to indicate outcomes of BC control strategies.

Radiation dose and second cancer risk in patients treated for cancer of the cervix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boice, J.D. Jr.; Engholm, G.; Kleinerman, R.A.

1988-10-01

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder (relative risk (RR) = 4.0),more » rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors.« less

Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency.

PubMed

Wasserstein, Melissa P; Jones, Simon A; Soran, Handrean; Diaz, George A; Lippa, Natalie; Thurberg, Beth L; Culm-Merdek, Kerry; Shamiyeh, Elias; Inguilizian, Haig; Cox, Gerald F; Puga, Ana Cristina

2015-01-01

Olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is an investigational enzyme replacement therapy (ERT) for patients with ASM deficiency [ASMD; Niemann-Pick Disease (NPD) A and B]. This open-label phase 1b study assessed the safety and tolerability of olipudase alfa using within-patient dose escalation to gradually debulk accumulated sphingomyelin and mitigate the rapid production of metabolites, which can be toxic. Secondary objectives were pharmacokinetics, pharmacodynamics, and exploratory efficacy. Five adults with nonneuronopathic ASMD (NPD B) received escalating doses (0.1 to 3.0 mg/kg) of olipudase alfa intravenously every 2 weeks for 26 weeks. All patients successfully reached 3.0mg/kg without serious or severe adverse events. One patient repeated a dose (2.0 mg/kg) and another had a temporary dose reduction (1.0 to 0.6 mg/kg). Most adverse events (97%) were mild and all resolved without sequelae. The most common adverse events were headache, arthralgia, nausea and abdominal pain. Two patients experienced single acute phase reactions. No patient developed hypersensitivity or anti-olipudase alfa antibodies. The mean circulating half-life of olipudase alfa ranged from 20.9 to 23.4h across doses without accumulation. Ceramide, a sphingomyelin catabolite, rose transiently in plasma after each dose, but decreased over time. Reductions in sphingomyelin storage, spleen and liver volumes, and serum chitotriosidase activity, as well as improvements in infiltrative lung disease, lipid profiles, platelet counts, and quality of life assessments, were observed. This study provides proof-of-concept for the safety and efficacy of within-patient dose escalation of olipudase alfa in patients with nonneuronopathic ASMD. Copyright © 2015. Published by Elsevier Inc.

Blood Pressure and Coronary Perfusion Pressure Targeted Cardiopulmonary Resuscitation Improves 24-Hour Survival from Ventricular Fibrillation Cardiac Arrest

PubMed Central

Maryam, Y.; Sutton, Robert M.; Friess, Stuart H.; Bratinov, George; Bhalala, Utpal; Kilbaugh, Todd J.; Lampe, Joshua; Nadkarni, Vinay M.; Becker, Lance B.; Berg, Robert A.

2016-01-01

Objective Treatment algorithms for cardiac arrest are rescuer-centric and vary little from patient to patient. The objective of this study was to determine if cardiopulmonary resuscitation (CPR) targeted to arterial blood pressure and coronary perfusion pressure (CPP) rather than optimal Guideline Care would improve 24-hour survival in a porcine model of ventricular fibrillation (VF) cardiac arrest. Design Randomized interventional study Setting Preclinical animal laboratory Subjects Female 3-month old swine Interventions/Measurements After induction of anesthesia and 7 minutes of untreated VF, 16 female 3-month old swine were randomized to: 1) Blood Pressure (BP) care: titration of chest compression (CC) depth to a systolic blood pressure (SBP) of 100 mmHg and vasopressor dosing to maintain CPP >20mmHg or 2) Guideline care: CC depth targeted to 51 mm and standard Guideline vasopressor dosing. Animals received manual CPR for 10 minutes before the first defibrillation attempt and standardized post-resuscitation care for 24 hours. Main Results 24-hour survival was more likely with BP care versus Guideline care (0/8 versus 5/8, p<0.03), and all survivors had normal neurological examinations. Mean CPP prior to defibrillation was significantly higher with BP care (28±3 mmHg versus 10±6 mmHg, p<0.01). CC depth was lower with BP care (48±0.4 mmHg versus 44±0.5 mmHg, p<0.05) and number of vasopressor doses was higher with BP care (median 3 [range 1-7] versus 2 [range 2-2], p<0.01). Conclusions Individualized goal-directed hemodynamic resuscitation targeting SBP of 100 mmHg and CPP >20 mmHg improved 24-hour survival compared to Guideline care in this model of VF cardiac arrest. PMID:27414479

Four-dimensional layer-stacking carbon-ion beam dose distribution by use of a lung numeric phantom.

PubMed

Mori, Shinichiro; Kumagai, Motoki; Miki, Kentaro

2015-07-01

To extend layer-stacking irradiation to accommodate intrafractional organ motion, we evaluated the carbon-ion layer-stacking dose distribution using a numeric lung phantom. We designed several types of range compensators. The planning target volume was calculated from the respective respiratory phases for consideration of intrafractional beam range variation. The accumulated dose distribution was calculated by registering of the dose distributions at respective phases to that at the reference phase. We evaluated the dose distribution based on the following six parameters: motion displacement, direction, gating window, respiratory cycle, range-shifter change time, and prescribed dose. All parameters affected the dose conformation to the moving target. By shortening of the gating window, dose metrics for superior-inferior (SI) and anterior-posterior (AP) motions were decreased from a D95 of 94 %, Dmax of 108 %, and homogeneity index (HI) of 23 % at T00-T90, to a D95 of 93 %, Dmax of 102 %, and HI of 20 % at T40-T60. In contrast, all dose metrics except the HI were independent of respiratory cycle. All dose metrics in SI motion were almost the same in respective motion displacement, with a D95 of 94 %, Dmax of 108 %, Dmin of 89 %, and HI of 23 % for the ungated phase, and D95 of 93 %, Dmax of 102 %, Dmin of 85 %, and HI of 20 % for the gated phase. The dose conformation to a moving target was improved by the gating strategy and by an increase in the prescribed dose. A combination of these approaches is a practical means of adding them to existing treatment protocols without modifications.

Long-Term Outcomes With Intraoperative Radiotherapy as a Component of Treatment for Locally Advanced or Recurrent Uterine Sarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barney, Brandon M., E-mail: barney.brandon@mayo.edu; Petersen, Ivy A.; Dowdy, Sean C.

2012-05-01

Purpose: To report our institutional experience with intraoperative radiotherapy (IORT) as a component of treatment for women with locally advanced or recurrent uterine sarcoma. Methods and Materials: From 1990 to 2010, 16 women with primary (n = 3) or locoregionally recurrent (n = 13) uterine sarcoma received IORT as a component of combined modality treatment. Tumor histology studies found leiomyosarcoma (n = 9), endometrial stromal sarcoma (n = 4), and carcinosarcoma (n = 3). Surgery consisted of gross total resection in 2 patients, subtotal resection in 6 patients, and resection with close surgical margins in 8 patients. The median IORTmore » dose was 12.5 Gy (range, 10-20 Gy). All patients received perioperative external beam radiotherapy (EBRT; median dose, 50.4 Gy; range, 20-62.5 Gy), and 6 patients also received perioperative systemic therapy. Results: Seven of the 16 patients are alive at a median follow-up of 44 months (range, 11-203 months). The 3-year Kaplan-Meier estimate of local relapse (within the EBRT field) was 7%, and central control (within the IORT field) was 100%. No local failures occurred in any of the 6 patients who underwent subtotal resection. The 3-year freedom from distant relapse was 48%, with failures occurring most frequently in the lungs or mediastinum. Median survival was 18 months, and 3-year Kaplan-Meier estimates of cause-specific and overall survival were 58% and 53%, respectively. Three patients (19%) experienced late Grade 3 toxicity. Conclusions: A combined modality approach with perioperative EBRT, surgery, and IORT for locally advanced or recurrent uterine sarcoma resulted in excellent local disease control with acceptable toxicity, even in patients with positive resection margins. With this approach, some patients were able to experience long-term freedom from recurrence.« less

Rectal Bleeding After High-Dose-Rate Brachytherapy Combined With Hypofractionated External-Beam Radiotherapy for Localized Prostate Cancer: The Relationship Between Dose-Volume Histogram Parameters and the Occurrence Rate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okamoto, Masahiko, E-mail: masaoka@showa.gunma-u.ac.jp; Ishikawa, Hitoshi; Ebara, Takeshi

2012-02-01

Purpose: To determine the predictive risk factors for Grade 2 or worse rectal bleeding after high-dose-rate brachytherapy (HDR-BT) combined with hypofractionated external-beam radiotherapy (EBRT) for prostate cancer using dose-volume histogram analysis. Methods and Materials: The records of 216 patients treated with HDR-BT combined with EBRT were analyzed. The treatment protocols for HDR-BT were 5 Gy Multiplication-Sign five times in 3 days or 7 Gy Multiplication-Sign three, 10.5 Gy Multiplication-Sign two, or 9 Gy Multiplication-Sign two in 2 days. The EBRT doses ranged from 45 to 51 Gy with a fractional dose of 3 Gy. Results: In 20 patients Grade 2more » or worse rectal bleeding developed, and the cumulative incidence rate was 9% at 5 years. By converting the HDR-BT and EBRT radiation doses into biologic effective doses (BED), the BED{sub 3} at rectal volumes of 5% and 10% in the patients who experienced bleeding were significantly higher than those in the remaining 196 patients. Univariate analysis showed that a higher rectal BED{sub 3-5%} and the use of fewer needles in brachytherapy were correlated with the incidence of bleeding, but BED{sub 3-5%} was found to be the only significant factor on multivariate analysis. Conclusions: The radiation dose delivered to small rectal lesions as 5% is important for predicting Grade 2 or worse rectal bleeding after HDR-BT combined with EBRT for prostate cancer.« less

A Study of the Carbohydrate-to-Insulin Ratio in Pregnant Women with Type 1 Diabetes on Pump Treatment.

PubMed

Bongiovanni, Marzia; Fresa, Raffaella; Visalli, Natalia; Bitterman, Olimpia; Suraci, Concetta; Napoli, Angela

2016-06-01

The aim of this study was to assess carbohydrate (CHO)-to-insulin ratio (CHO/IR) values in pregnant women with type 1 diabetes and to describe differences in CHO/IR across each week of pregnancy. This was a multicenter, retrospective, observational study (2006-2012) of 101 white pregnant women with a mean age of 32 (range, 18-43) years who had type 1 diabetes and were under continuous subcutaneous insulin infusion (CSII) therapy. These patients had the following characteristics: type 1 diabetes duration was 1 year (range, 1-31 years), the pregestational glycosylated hemoglobin level was 6.9% (range, 6.8-12.1%), the median weight gain during pregnancy was 14 kg (-3; 25 kg), with delivery at 37 weeks (range, 30-40 weeks), and the child had a birth weight of 3.530 kg (range, 1.480-5.250 kg). The CHO/IR was measured by dividing the CHO (in g) of each meal by insulin unit injected to acquire and maintain the following glycemic targets: fasting <90 mg/dL and 1-h postprandial <130 mg/dL. Simultaneously, CHO/IR indices were calculated through 500/total daily doses of insulin and 300/total daily doses of insulin. Education and management before and during pregnancy were in agreement with Italian Association of Dietitians, Association of Medical Diabetologists, and Italian Society of Diabetology recommendations. Data were analyzed using SPSS software (version 20.0; SPSS, Inc., Chicago, IL). The CHO/IR decreased on average from 9.6 (5-18) to 5.4 (2.3-8) at breakfast, from 10 (3.5-16) to 8.4 (3.0-17.8) at lunch, and from 12.5 (8-20) to 6.1 (4.2-12) at dinner. The CHO/IR calculated using the "500 rule" decreased from 14.3 (10-20.3) to 8.6 (4.1-15.9). Using the "300 rule," the ratios decreased from 8.5 (6-12.1) to 5.2 (2.4-9.5). The bivariate correlation between the values calculated more appropriate values using the "300 rule" for breakfast and the "500 rule" for lunch and dinner across all weeks of pregnancy. CHO/IR reduction in pregnancy is likely due to an increase in insulin resistance.

Multichannel dosemeter and Al2O3:C optically stimulated luminescence fibre sensors for use in radiation therapy: evaluation with electron beams.

PubMed

Magne, S; Auger, L; Bordy, J M; de Carlan, L; Isambert, A; Bridier, A; Ferdinand, P; Barthe, J

2008-01-01

This article proposes an innovative multichannel optically stimulated luminescence (OSL) dosemeter for on-line in vivo dose verification in radiation therapy. OSL fibre sensors incorporating small Al(2)O(3):C fibre crystals (TLD(500)) have been tested with an X-ray generator. A reproducible readout procedure should reduce the fading-induced uncertainty ( approximately - 1% per decade). OSL readouts are temperature-dependent [ approximately 0.3% K(-1) when OSL stimulation is performed at the same temperature as irradiation; approximately 0.16% K(-1) after thermalisation (20 degrees C)]. Sensor calibration and depth-dose measurements with electron beams have been performed with a Saturne 43 linear accelerator in reference conditions at CEA-LNHB (ionising radiation reference laboratory in France). Predosed OSL sensors show a good repeatability in multichannel operation and independence versus electron energy in the range (9, 18 MeV). The difference between absorbed doses measured by OSL and an ionisation chamber were within +/-0.9% (for a dose of about 1 Gy) despite a sublinear calibration curve.

Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low–dose rate delivery techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jie; Lang, Jinyi; Wang, Pei

2014-01-01

Reirradiation of patients who were previously treated with radiotherapy is vastly challenging. Pulsed low–dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while providing significant tumor control for recurrent cancers. This work investigates treatment planning techniques for intensity-modulated radiation therapy (IMRT)-based PLDR treatment of various sites, including cases with pancreatic and prostate cancer. A total of 20 patients with clinical recurrence were selected for this study, including 10 cases with pancreatic cancer and 10 with prostate cancer. Large variations in the target volume were included to test the ability of IMRT using the existing treatmentmore » planning system and optimization algorithm to deliver uniform doses in individual gantry angles/fields for PLDR treatments. Treatment plans were generated with 10 gantry angles using the step-and-shoot IMRT delivery technique, which can be delivered in 3-minute intervals to achieve an effective low dose rate of 6.7 cGy/min. Instead of dose constraints on critical structures, ring structures were mainly used in PLDR-IMRT optimization. In this study, the PLDR-IMRT plans were compared with the PLDR-3-dimensional conformal radiation therapy (3DCRT) plans and the PLDR-RapidArc plans. For the 10 cases with pancreatic cancer that were investigated, the mean planning target volume (PTV) dose for each gantry angle in the PLDR-IMRT plans ranged from 17.6 to 22.4 cGy. The maximum doses ranged between 22.9 and 34.8 cGy. The minimum doses ranged from 8.2 to 17.5 cGy. For the 10 cases with prostate cancer that were investigated, the mean PTV doses for individual gantry angles ranged from 18.8 to 22.6 cGy. The maximum doses per gantry angle were between 24.0 and 34.7 cGy. The minimum doses per gantry angle ranged from 4.4 to 17.4 cGy. A significant reduction in the organ at risk (OAR) dose was observed with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. The volume receiving an 18-Gy (V{sub 18}) dose for the left and right kidneys was reduced by 10.6% and 12.5%, respectively, for the pancreatic plans. The volume receiving a 45-Gy (V{sub 45}) dose for the small bowel decreased from 65.3% to 45.5%. For the cases with prostate cancer, the volume receiving a 40-Gy (V{sub 40}) dose for the bladder and the rectum was reduced significantly by 25.1% and 51.2%, respectively. When compared with the RapidArc technique, the volume receiving a 30-Gy (V{sub 30}) dose for the left and the right kidneys was lower in the IMRT plans. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. These results clearly demonstrated that the PLDR-IMRT plan was suitable for PLDR pancreatic and prostate cancer treatments in terms of the overall plan quality. A significant reduction in the OAR dose was achieved with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. When compared with the PLDR-3DCRT plan, the PLDR-IMRT plan could provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent pancreatic and prostate cancers. The PLDR-IMRT plan is an effective treatment choice for recurrent cancers in most cancer centers.« less

[Optimization of the dose of radiation in shoulder arthrography].

PubMed

Campos, P A; Redondo, M V; Berná-Serna, J D; Reus, M; Martínez, F

2009-01-01

The aim of this study was to determine whether using a film with radiopaque coordinates placed over the region of interest to guide shoulder arthrography can reduce the dose of radiation received by patients. The entrance dose was obtained in 34 patients (mean age, 44 years; range, 15 to 75 years). The dose received by organs at risk and the effective dose were estimated with Monte Carlo techniques using the following input parameters: patient anatomy, examination geometry, and air kerma at the entrance to the patient without backscattering. Arthrography was performed with a remote controlled device and images were acquired digitally without fluoroscopy. The mean thickness of the shoulders studied was 14.6+/-2.1cm (9-20 cm). Images were obtained with 80+/-10 kVp (60-85 kVp) and 6.5+/-3.5 mAs (1.4-17 mAs). The mean time of irradiation for each patient was 20+/-6 ms (6.9-47.9 ms). The calculated air kerma was 0.41+/-0.19 mGy and the effective dose was 0.79+/-0.40 muSv. The technique described in this study has enabled us to reduce the dose of radiation received by patients undergoing shoulder arthrography in comparison with other techniques described in the literature and to ensure that the radiologist performing the procedure is not irradiated.

[Efficacy of intravenous phenobarbital treatment for status epilepticus].

PubMed

Muramoto, Emiko; Mizobuchi, Masahiro; Sumi, Yoshihiro; Sako, Kazuya; Nihira, Atsuko; Takeuchi, Akiko; Nakamura, Hirohiko

2013-08-01

Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.

Analytical modeling of relative luminescence efficiency of Al2O3:C optically stimulated luminescence detectors exposed to high-energy heavy charged particles.

PubMed

Sawakuchi, Gabriel O; Yukihara, Eduardo G

2012-01-21

The objective of this work is to test analytical models to calculate the luminescence efficiency of Al(2)O(3):C optically stimulated luminescence detectors (OSLDs) exposed to heavy charged particles with energies relevant to space dosimetry and particle therapy. We used the track structure model to obtain an analytical expression for the relative luminescence efficiency based on the average radial dose distribution produced by the heavy charged particle. We compared the relative luminescence efficiency calculated using seven different radial dose distribution models, including a modified model introduced in this work, with experimental data. The results obtained using the modified radial dose distribution function agreed within 20% with experimental data from Al(2)O(3):C OSLDs relative luminescence efficiency for particles with atomic number ranging from 1 to 54 and linear energy transfer in water from 0.2 up to 1368 keV µm(-1). In spite of the significant improvement over other radial dose distribution models, understanding of the underlying physical processes associated with these radial dose distribution models remain elusive and may represent a limitation of the track structure model.

Integral radiation dose to normal structures with conformal external beam radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aoyama, Hidefumi; Westerly, David Clark; Mackie, Thomas Rockwell

2006-03-01

Background: This study was designed to evaluate the integral dose (ID) received by normal tissue from intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Twenty-five radiation treatment plans including IMRT using a conventional linac with both 6 MV (6MV-IMRT) and 20 MV (20MV-IMRT), as well as three-dimensional conformal radiotherapy (3DCRT) using 6 MV (6MV-3DCRT) and 20 MV (20MV-3DCRT) and IMRT using tomotherapy (6MV) (Tomo-IMRT), were created for 5 patients with localized prostate cancer. The ID (mean dose x tissue volume) received by normal tissue (NTID) was calculated from dose-volume histograms. Results: The 6MV-IMRT resulted in 5.0% lower NTID thanmore » 6MV-3DCRT; 20 MV beam plans resulted in 7.7%-11.2% lower NTID than 6MV-3DCRT. Tomo-IMRT NTID was comparable to 6MV-IMRT. Compared with 6MV-3DCRT, 6MV-IMRT reduced IDs to the rectal wall and penile bulb by 6.1% and 2.7%, respectively. Tomo-IMRT further reduced these IDs by 11.9% and 16.5%, respectively. The 20 MV did not reduce IDs to those structures. Conclusions: The difference in NTID between 3DCRT and IMRT is small. The 20 MV plans somewhat reduced NTID compared with 6 MV plans. The advantage of tomotherapy over conventional IMRT and 3DCRT for localized prostate cancer was demonstrated in regard to dose sparing of rectal wall and penile bulb while slightly decreasing NTID as compared with 6MV-3DCRT.« less

Reference dosimetry using radiochromic film

PubMed Central

Girard, Frédéric; Bouchard, Hugo

2012-01-01

The objectives of this study are to identify and quantify factors that influence radiochromic film dose response and to determine whether such films are suitable for reference dosimetry. The influence of several parameters that may introduce systematic dose errors when performing reference dose measurements were investigated. The effect of the film storage temperature was determined by comparing the performance of three lots of GAFCHROMIC EBT2 films stored at either 4°C or room temperature. The effect of high (>80%) or low (<20%) relative humidity was also determined. Doses measured in optimal conditions with EBT and EBT2 films were then compared with an A12 ionization chamber measurement. Intensity‐modulated radiation therapy quality controls using EBT2 films were also performed in reference dose. The results obtained using reference dose measurements were compared with those obtained using relative dose measurements. Storing the film at 4°C improves the stability of the film over time, but does not eliminate the noncatalytic film development, seen as a rise in optical density over time in the absence of radiation. Relative humidity variations ranging from 80% to 20% have a strong impact on the optical density and could introduce dose errors of up to 15% if the humidity were not controlled during the film storage period. During the scanning procedure, the film temperature influences the optical density that is measured. When controlling for these three parameters, the dose differences between EBT or EBT2 and the A12 chamber are found to be within ±4% (2σ level) over a dose range of 20–350 cGy. Our results also demonstrate the limitation of the Anisotropic Analytical Algorithm for dose calculation of highly modulated treatment plans. PACS numbers: 87.55.Qr; 87.56.Fc PMID:23149793

SU-E-J-146: A Research of PET-CT SUV Range for the Online Dose Verification in Carbon Ion Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, L; Hu, W; Moyers, M

2015-06-15

Purpose: Positron-emitting isotope distributions can be used for the image fusion of the carbon ion planning CT and online target verification PETCT, after radiation in the same decay period,the relationship between the same target volume and the SUV value of different every single fraction dose can be found,then the range of SUV for the radiation target could be decided.So this online range also can provide reference for the correlation and consistency in planning target dose verification and evaluation for the clinical trial. Methods: The Rando head phantom can be used as real body,the 10cc cube volume target contouring is done,beammore » ISO Center depth is 7.6cm and the 90 degree fixed carbon ion beams should be delivered in single fraction effective dose of 2.5GyE,5GyE and 8GyE.After irradiation,390 seconds later the 30 minutes PET-CT scanning is performed,parameters are set to 50Kg virtual weight,0.05mCi activity.MIM Maestro is used for the image processing and fusion,five 16mm diameter SUV spheres have been chosen in the different direction in the target.The average SUV in target for different fraction dose can be found by software. Results: For 10cc volume target,390 seconds decay period,the Single fraction effective dose equal to 2.5Gy,Ethe SUV mean value is 3.42,the relative range is 1.72 to 6.83;Equal to 5GyE,SUV mean value is 9.946,the relative range is 7.016 to 12.54;Equal or above to 8GyE,SUV mean value is 20.496,the relative range is 11.16 to 34.73. Conclusion: Making an evaluation for accuracy of the dose distribution using the SUV range which is from the planning CT with after treatment online PET-CT fusion for the normal single fraction carbon ion treatment is available.Even to the plan which single fraction dose is above 2GyE,in the condition of other parameters all the same,the SUV range is linearly dependent with single fraction dose,so this method also can be used in the hyper-fraction treatment plan.« less

The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

PubMed

Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

2017-07-01

To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

Comparison of linac-based fractionated stereotactic radiotherapy and tomotherapy treatment plans for intra-cranial tumors

NASA Astrophysics Data System (ADS)

Jang, Bo Shim; Suk, Lee; Sam, Ju Cho; Sang, Hoon Lee; Juree, Kim; Kwang, Hwan Cho; Chul, Kee Min; Hyun Do, Huh; Rena, Lee; Dae, Sik Yang; Young, Je Park; Won, Seob Yoon; Chul, Yong Kim; Soo, Il Kwon

2010-11-01

This study compares and analyzes stereotactic radiotherapy using tomotherapy and linac-based fractionated stereotactic radiotherapy in the treatment of intra-cranial tumors, according to some cases. In this study, linac-based fractionated stereotactic radiotherapy and tomotherapy treatment were administered to five patients diagnosed with intra-cranial cancer in which the dose of 18-20 Gy was applied on 3-5 separate occasions. The tumor dosing was decided by evaluating the inhomogeneous index (II) and conformity index (CI). Also, the radiation-sensitive tissue was evaluated using low dose factors V1, V2, V3, V4, V5, and V10, as well as the non-irradiation ratio volume (NIV). The values of the II for each prescription dose in the linac-based non-coplanar radiotherapy plan and tomotherapy treatment plan were (0.125±0.113) and (0.090±0.180), respectively, and the values of the CI were (0.899±0.149) and (0.917±0.114), respectively. The low dose areas, V1, V2, V3, V4, V5, and V10, in radiation-sensitive tissues in the linac-based non-coplanar radiotherapy plan fell into the ranges 0.3%-95.6%, 0.1%-87.6%, 0.1%-78.8%, 38.8%-69.9%, 26.6%-65.2%, and 4.2%-39.7%, respectively, and the tomotherapy treatment plan had ranges of 13.6%-100%, 3.5%-100%, 0.4%-94.9%, 0.2%-82.2%, 0.1%-78.5%, and 0.3%-46.3%, respectively. Regarding the NIV for each organ, it is possible to obtain similar values except for the irradiation area of the brain stem. The percentages of NIV 10%, NIV20%, and NIV30%for the brain stem in each patient were 15%-99.8%, 33.4%-100%, and 39.8%-100%, respectively, in the fractionated stereotactic treatment plan and 44.2%-96.5%, 77.7%-99.8%, and 87.8%-100%, respectively, in the tomotherapy treatment plan. In order to achieve higher-quality treatment of intra-cranial tumors, treatment plans should be tailored according to the isodose target volume, inhomogeneous index, conformity index, position of the tumor upon fractionated stereotactic radiosurgery, and radiation dosage for radiation-sensitive tissues.

Long-Term Pulmonary Function in Survivors of Childhood Cancer

PubMed Central

Armenian, Saro H.; Landier, Wendy; Francisco, Liton; Herrera, Claudia; Mills, George; Siyahian, Aida; Supab, Natt; Wilson, Karla; Wolfson, Julie A.; Horak, David; Bhatia, Smita

2015-01-01

Purpose This study was undertaken to determine the magnitude of pulmonary dysfunction in childhood cancer survivors when compared with healthy controls and the extent (and predictors) of decline over time. Patients and Methods Survivors underwent baseline (t1) pulmonary function tests, followed by a second comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3 years). Survivors were also compared with age- and sex-matched healthy controls at t2. Results Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9 years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years). Compared with odds for healthy controls, the odds of restrictive defects were increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to 15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0; 95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR, 5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and chest radiation dose (referent: no chest radiation; ≤ 20 Gy: OR, 6.4; 95% CI, 1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were associated with diffusion abnormalities. Among survivors with normal pulmonary function tests at t1, females and survivors treated with more than 20 Gy chest radiation demonstrated decline in diffusion function over time. Conclusion Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly more likely to have restrictive and diffusion defects when compared with healthy controls. Diffusion capacity declines with time after exposure to pulmonary-toxic therapy, particularly among females and survivors treated with high-dose chest radiation. These individuals could benefit from subsequent monitoring. PMID:25847925

Drug Dose Per Kilogram Lean Body Mass Predicts Hematologic Toxicity From Carboplatin-Doublet Chemotherapy in Advanced Non-Small-Cell Lung Cancer.

PubMed

Sjøblom, Bjørg; Benth, Jūratė Šaltytė; Grønberg, Bjørn H; Baracos, Vickie E; Sawyer, Michael B; Fløtten, Øystein; Hjermstad, Marianne J; Aass, Nina; Jordhøy, Marit

2017-03-01

Variations in lean body mass (LBM) have been suggested to explain variations in toxicity from systemic cancer treatment. We investigated if drug doses per kilogram of LBM were associated with severe hematologic toxicity (HT) in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) enrolled onto randomized trials comparing first-line carboplatin-doublets. Patients received carboplatin (AUC [area under the plasma concentration vs. time curve] = 5) plus either pemetrexed 500 mg/m 2 , gemcitabine 1000 mg/m 2 , or vinorelbine 60 mg/m 2 . LBM was estimated from the cross-sectional muscle area at the third lumbar vertebra on computed tomographic scans. Administered doses on day 1, first cycle, were recalculated as milligram of drug per kilogram of LBM. Primary outcome was Common Terminology Criteria for Adverse Events version 3.0 grade 3/4 HT after cycle 1. Data from 424 patients were analyzed. Mean age was 65 years, 57% were men, and 78% had stage IV disease. Despite dose individualization by body surface area for the nonplatinum drugs, mean (range) doses expressed as mg/kg LBM showed ∼3-fold range: gemcitabine 38.0 (22.5-61.7) mg/kg LBM, pemetrexed 19.1 (8.1-27.9) mg/kg LBM, and vinorelbine 2.4 (1.4-3.6) mg/kg LBM. For these drugs, dose per kilogram of LBM was associated with HT in adjusted multivariate models (P = .004). Taking mean dose per kilogram LBM for each drug as reference, a 1% increase (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.01-1.06) or 1% decrease (OR = 0.97; 95% CI, 0.95-0.99) was associated with altered risk of grade 3/4 HT. For doses > 20% above and below mean (14% and 15% of patients, respectively) the risk of grade 3/4 HT was almost doubled (OR = 1.93, 95% CI, 1.21-3.10) and halved (OR = 0.52; 95% CI, 0.32-0.83), respectively. Dose per kilogram of LBM varied considerably and was an independent predictor of HT. Computed tomography-defined LBM may provide a future basis for better dose individualization. Copyright © 2016 Elsevier Inc. All rights reserved.

Radioprotective effect of polyethylene glycol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaeffer, J.; Schellenberg, K.A.; Seymore, C.H.

1986-07-01

Polyethylene glycol of molecular weight 400 (PEG-400) had a radioprotective effect of about 20% against lethality when given ip 20 min prior to single or fractionated X-ray doses to the head and neck. Dose modification factors (DMF) based on LD50/15 values ranged from 1.14 to 1.24. A similar DMF of 1.12 based on LD50/30 values was obtained using single doses of whole-body X irradiation. Mice given head and neck irradiation had significantly reduced rectal temperatures (31.3 +/- 3.0/sup 0/C) 9 days post irradiation compared with unirradiated controls (35.4 +/- 0.6/sup 0/C). No such reduction was observed when PEG-400 was givenmore » with radiation (36.3 +/- 0.9/sup 0/C). PEG-400 also lessened, but not significantly, the frequency of shivering in irradiated animals. Histopathologic examination of the oral structures demonstrated only marginal protection by PEG-400. Estimation of the alpha/beta ratio from LD50 data on head and neck-irradiated mice yielded values of 4.4 +/- 1.9 (95% confidence limits) Gy without PEG-400 and 7.9 +/- 1.4 Gy with PEG-400. Since it is a non-thiol radioprotector, PEG-400 may be more useful when combined with more conventional thiol-containing radioprotectors.« less

Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial.

PubMed

Heery, Christopher R; O'Sullivan-Coyne, Geraldine; Madan, Ravi A; Cordes, Lisa; Rajan, Arun; Rauckhorst, Myrna; Lamping, Elizabeth; Oyelakin, Israel; Marté, Jennifer L; Lepone, Lauren M; Donahue, Renee N; Grenga, Italia; Cuillerot, Jean-Marie; Neuteboom, Berend; Heydebreck, Anja von; Chin, Kevin; Schlom, Jeffrey; Gulley, James L

2017-05-01

Avelumab (MSB0010718C) is a human IgG1 monoclonal antibody that binds to PD-L1, inhibiting its binding to PD-1, which inactivates T cells. We aimed to establish the safety and pharmacokinetics of avelumab in patients with solid tumours while assessing biological correlatives for future development. This open-label, single-centre, phase 1a, dose-escalation trial (part of the JAVELIN Solid Tumor trial) assessed four doses of avelumab (1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg), with dose-level cohort expansions to provide additional safety, pharmacokinetics, and target occupancy data. This study used a standard 3 + 3 cohort design and assigned patients sequentially at trial entry according to the 3 + 3 dose-escalation algorithm and depending on the number of dose-limiting toxicities during the first 3-week assessment period (the primary endpoint). Patient eligibility criteria included age 18 years or older, Eastern Cooperative Oncology Group performance status 0-1, metastatic or locally advanced previously treated solid tumours, and adequate end-organ function. Avelumab was given as a 1-h intravenous infusion every 2 weeks. Patients in the dose-limiting toxicity analysis set were assessed for the primary endpoint of dose-limiting toxicity, and all patients enrolled in the dose-escalation part were assessed for the secondary endpoints of safety (treatment-emergent and treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0), pharmacokinetic and pharmacodynamic profiles (immunological effects), best overall response by Response Evaluation Criteria, and antidrug antibody formation. The population for the pharmacokinetic analysis included a subset of patients with rich pharmacokinetic samples from two selected disease-specific expansion cohorts at the same study site who had serum samples obtained at multiple early timepoints. This trial is registered with ClinicalTrials.gov, number NCT01772004. Patient recruitment to the dose-escalation part reported here is closed. Between Jan 31, 2013, and Oct 8, 2014, 53 patients were enrolled (four patients at 1 mg/kg, 13 at 3 mg/kg, 15 at 10 mg/kg, and 21 at 20 mg/kg). 18 patients were analysed in the dose-limiting toxicity analysis set: three at dose level 1 (1 mg/kg), three at dose level 2 (3 mg/kg), six at dose level 3 (10 mg/kg), and six at dose level 4 (20 mg/kg). Only one dose-limiting toxicity occurred, at the 20 mg/kg dose, and thus the maximum tolerated dose was not reached. In all 53 enrolled patients (the safety analysis set), common treatment-related adverse events (occurring in >10% of patients) included fatigue (21 patients [40%]), influenza-like symptoms (11 [21%]), fever (8 [15%]), and chills (6 [11%]). Grade 3-4 treatment-related adverse events occurred in nine (17%) of 53 patients, with autoimmune disorder (n=3), increased blood creatine phosphokinase (n=2), and increased aspartate aminotransferase (n=2) each occurring in more than one patient (autoimmune disorder in two patients at 10 mg/kg and one patient at 20 mg/kg, increased blood creatine phosphokinase in two patients at 20 mg/kg, and increased aspartate aminotransferase in one patient at 1 mg/kg, and one patient at 10 mg/kg). Six (11%) of 53 patients had a serious treatment-related adverse event: autoimmune disorder (two [13%]), lower abdominal pain (one [7%]), fatigue (one [7%]), and influenza-like illness (one [7%]) in three patients treated at 10 mg/kg dose level, and autoimmune disorder (one [5%]), increased amylase (one [5%]), myositis (one [5%]), and dysphonia (one [5%]) in three patients who received the 20 mg/kg dose. We recorded some evidence of clinical activity in various solid tumours, with partial confirmed or unconfirmed responses in four (8%) of 53 patients; 30 (57%) additional patients had stable disease. Pharmacokinetic analysis (n=86) showed a dose-proportional exposure between doses of 3 mg/kg and 20 mg/kg and a half-life of 95-99 h (3·9-4·1 days) at the 10 mg/kg and 20 mg/kg doses. Target occupancy was greater than 90% at doses of 3 mg/kg and 10 mg/kg. Antidrug antibodies were detected in two (4%) of 53 patients. No substantial differences were found in absolute lymphocyte count or multiple immune cell subsets, including those expressing PD-L1, after treatment with avelumab. 31 (58%) of 53 patients in the overall safety population died; no deaths were related to treatment on study. Avelumab has an acceptable toxicity profile up to 20 mg/kg and the maximum tolerated dose was not reached. Based on pharmacokinetics, target occupancy, and immunological analysis, we chose 10 mg/kg every 2 weeks as the dose for further development and phase 3 trials are ongoing. National Cancer Institute and Merck KGaA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of Residual Tumor Volume and Radiation Dose Coverage in Outcomes for Clival Chordoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com; Indiana University Health Proton Therapy Center, Bloomington, Indiana; Linton, Okechukwu R.

2016-05-01

Purpose: The purpose of this study was to evaluate factors associated with tumor control in clival chordomas. Methods and Materials: A retrospective review of 39 patients treated with surgery and proton therapy for clival chordomas between 2004 and 2014 was performed. The median prescribed dose was 77.4 Gy (relative biological effectiveness [RBE]); range was 70.2-79.2 Gy (RBE). Minimum and median doses to gross tumor volume (GTV), radiation dose received by 1 cm{sup 3} of GTV (D1cm{sup 3}), and the equivalent uniform dose were calculated. Receiver operating characteristics curves evaluated the predictive sensitivity and specificity for local failure of potential cutpoint values for GTVmore » and D1cm{sup 3}. Results: After a median follow-up of 51 months, the 5-year estimate of local control (LC) was 69.6% (95% confidence interval [CI] 50.0%-89.2%), and overall survival (OS) was 81.4% (95% CI: 65.3%-97.5%). Tumor histology, GTV at the time of radiation, and prescribed radiation dose were significantly associated with local control on multivariate analysis, whereas D1cm{sup 3} was associated with overall survival. Compared to those patients whose conditions remained controlled, patients experiencing tumor failure had statistically significant larger GTVs and lower D1cm{sup 3}, and prescribed and median doses to GTV. A subset of 21 patients with GTV of ≤20 cm{sup 3} and D1cm{sup 3} of >67 Gy (RBE) had a median follow-up of 47 months. The 5-year estimate of local control in this subset was 81.1% (95% CI: 61.7%-100%; P=.004, overall comparison by GTV ≤20 cm{sup 3} stratified by D1cm{sup 3}). A D1cm{sup 3} of 74.5 Gy (RBE) had 80% sensitivity for local control and 60% specificity, whereas a GTV of 9.3 cm{sup 3} had 80% sensitivity for local control and 66.7% specificity. Conclusions: Local control of clival chordomas was associated with both smaller size of residual tumor and more complete high-dose coverage of residual tumor. Multidisciplinary care should seek maximal safe surgical resection, particularly to facilitate delivery of high-dose radiation therapy in proximity to critical structures. A D1cm{sup 3} ≥74.5 Gy (RBE) represents a proposed treatment planning objective.« less

Photodynamic therapy with PhotoPoint photosensitiser MV6401, indium chloride methyl pyropheophorbide, achieves selective closure of rat corneal neovascularisation and rabbit choriocapillaris

PubMed Central

Ciulla, T A; Criswell, M H; Snyder, W J; Small, W

2005-01-01

Aim: The new photosensitiser PhotoPoint MV6401, indium chloride methyl pyropheophorbide, was assessed as a possible ocular photodynamic therapy agent in a rat model of experimentally induced corneal neovascularisation and in choriocapillaris closure in the rabbit. Optimal drug and light activation parameters were determined. Methods: MV6401 (Miravant Pharmaceuticals, Inc, Santa Barbara, CA, USA) was activated at 664 nm using a DD3-0665 (Miravant Systems Inc) 0.5 W diode laser. Corneal neovascularisation in rats was induced using an N-heptanol technique. The evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.01–0.1 μmol/kg, 5–25 J/cm2, and 10–60 minutes, respectively. The efficacy of MV6401 on normal choriocapillaris and choroidal vessels was evaluated in rabbits with indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. In rabbits, the evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.025–0.25 μmol/kg, 3.3–20 J/cm2, and 10 minutes, respectively. Results: In the rat corneal neovascularisation model, an optimal intravenous drug dosage of 0.075 μmol/kg was activated by a 20 J/cm2 light dose at 10 minutes after drug administration, the results of which demonstrated early evidence of efficacy in ocular neovascularisation. In rabbits, closure of the normal choriocapillaris was selectively achieved at a drug dosage of 0.15 μmol/kg using light doses from 3.3 to 20 J/cm2. Conclusion: PhotoPoint MV6401 is a potent photosensitiser that demonstrates both efficacy and selectivity in experimental ocular models. PMID:15615758

Photodynamic therapy with PhotoPoint photosensitiser MV6401, indium chloride methyl pyropheophorbide, achieves selective closure of rat corneal neovascularisation and rabbit choriocapillaris.

PubMed

Ciulla, T A; Criswell, M H; Snyder, W J; Small, W

2005-01-01

The new photosensitiser PhotoPoint MV6401, indium chloride methyl pyropheophorbide, was assessed as a possible ocular photodynamic therapy agent in a rat model of experimentally induced corneal neovascularisation and in choriocapillaris closure in the rabbit. Optimal drug and light activation parameters were determined. MV6401 (Miravant Pharmaceuticals, Inc, Santa Barbara, CA, USA) was activated at 664 nm using a DD3-0665 (Miravant Systems Inc) 0.5 W diode laser. Corneal neovascularisation in rats was induced using an N-heptanol technique. The evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.01-0.1 micromol/kg, 5-25 J/cm(2), and 10-60 minutes, respectively. The efficacy of MV6401 on normal choriocapillaris and choroidal vessels was evaluated in rabbits with indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. In rabbits, the evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.025-0.25 micromol/kg, 3.3-20 J/cm(2), and 10 minutes, respectively. In the rat corneal neovascularisation model, an optimal intravenous drug dosage of 0.075 micromol/kg was activated by a 20 J/cm(2) light dose at 10 minutes after drug administration, the results of which demonstrated early evidence of efficacy in ocular neovascularisation. In rabbits, closure of the normal choriocapillaris was selectively achieved at a drug dosage of 0.15 micromol/kg using light doses from 3.3 to 20 J/cm(2). PhotoPoint MV6401 is a potent photosensitiser that demonstrates both efficacy and selectivity in experimental ocular models.

Use of GnRH agonist implants for long-term suppression of fertility in extensively managed heifers and cows.

PubMed

D'Occhio, Michael J; Fordyce, Geoffry; Whyte, Tim R; Jubb, Tristan F; Fitzpatrick, Lee A; Cooper, Neil J; Aspden, William J; Bolam, Matt J; Trigg, Timothy E

2002-12-16

The ability of gonadotrophin releasing hormone (GnRH) agonist implants to suppress ovarian activity and prevent pregnancies, long-term, was examined in heifers and cows maintained under extensive management. At three cattle stations, heifers (2-year-old) and older cows (3- to 16-year-old) were assigned to a control group that received no treatment, or were treated with high-dose (12 mg, Station A) or low-dose (8 mg, Station B and Station C) GnRH agonist implants. The respective numbers of control and GnRH agonist-treated animals (heifers + cows) at each station were: Station A, 20 and 99; Station B, 19 and 89; Station C, 20 and 76. Animals were maintained with 4% bulls and monitored for pregnancy at 2-monthly intervals for approximately 12 months. Pregnancy rates for control heifers and control cows ranged from 60-90% and 80-100%, respectively, depending on the study site. The respective number of animals (heifers + cows) treated with GnRH agonist that conceived, and days to first conception, were: Station A, 9 (9%) and 336 +/- 3 days; Station B, 8 (10%) and 244 +/- 13 days; Station C, 20 (26%) and 231 +/- 3 days. Treatment with high-dose GnRH agonist prevented pregnancies for longer (approximately 300 days) than treatment with low-dose GnRH agonist (approximately 200 days). In the majority of heifers and cows treated with GnRH agonist, ovarian follicular growth was restricted to early antral follicles (2-4mm). The findings indicate that GnRH agonist implants have considerable potential as a practical technology to suppress ovarian activity and control reproduction in female cattle maintained in extensive rangelands environments. The technology also has broader applications in diverse cattle production systems. Copyright 2002 Elsevier Science B.V.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cazzato, Roberto Luigi, E-mail: gigicazzato@hotmail.it; Garnon, Julien, E-mail: juleiengarnon@gmail.com; Ramamurthy, Nitin, E-mail: nitin-ramamurthy@hotmail.com

AimTo review our preliminary experience with 6-l-18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT-guided radiofrequency ablation (RFA) of liver metastases from neuroendocrine tumours (NETs).Materials and MethodsThree patients (mean age 51.3 years; range 43–56) with gastro-entero pancreatic NET (GEP-NET) liver metastases underwent 18F-FDOPA PET/CT-guided RFA. Patients were referred with oligometastatic hepatic-confined disease (1–6 metastases; <3 cm) on 18F-FDOPA PET/CT; poor lesion visualisation on US, CT, and MR; and ongoing symptoms. Procedures were performed in an interventional PET/CT scanner under general anaesthesia using a split-dose protocol. Lesion characteristics, procedural duration and technical success (accurate probe placement and post-procedural ablation-zone photopaenia), complications, patient and operator dose, and clinical outcomes weremore » evaluated.ResultsThirteen liver metastases (mean size 11.4 mm, range 8–16) were treated in three patients (two presented with “carcinoid syndrome”). Technical success was 100 % with a mean procedural duration of 173.3 min (range 90–210) and no immediate complications. Mean patient dose was 2844 mGy·cm (range 2104–3686). Operator and radiographer doses were acceptable other than the operator’s right hand in the first case (149 µSv); this normalised in the second case. There was no local tumour or extra-hepatic disease progression at mid-term follow-up (mean 12.6 months; range 6–20); however, two cases progressed with new liver metastases at different sites. There was 100 % clinical success (n = 2) in resolving carcinoid syndrome symptoms.Conclusion18F-FDOPA PET/CT-guided RFA appears technically feasible, safe, and effective in patients with GEP-NETs and low-burden hepatic metastases. Further prospective studies are required to elucidate its precise role in tailored multimodality management of GEP-NET liver metastases.« less

Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

PubMed Central

Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

2012-01-01

Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

Monte Carlo modeling of HD120 multileaf collimator on Varian TrueBeam linear accelerator for verification of 6X and 6X FFF VMAT SABR treatment plans

PubMed Central

Gete, Ermias; Duzenli, Cheryl; Teke, Tony

2014-01-01

A Monte Carlo (MC) validation of the vendor‐supplied Varian TrueBeam 6 MV flattened (6X) phase‐space file and the first implementation of the Siebers‐Keall MC MLC model as applied to the HD120 MLC (for 6X flat and 6X flattening filterfree (6X FFF) beams) are described. The MC model is validated in the context of VMAT patient‐specific quality assurance. The Monte Carlo commissioning process involves: 1) validating the calculated open‐field percentage depth doses (PDDs), profiles, and output factors (OF), 2) adapting the Siebers‐Keall MLC model to match the new HD120‐MLC geometry and material composition, 3) determining the absolute dose conversion factor for the MC calculation, and 4) validating this entire linac/MLC in the context of dose calculation verification for clinical VMAT plans. MC PDDs for the 6X beams agree with the measured data to within 2.0% for field sizes ranging from 2 × 2 to 40 × 40 cm2. Measured and MC profiles show agreement in the 50% field width and the 80%‐20% penumbra region to within 1.3 mm for all square field sizes. MC OFs for the 2 to 40 cm2 square fields agree with measurement to within 1.6%. Verification of VMAT SABR lung, liver, and vertebra plans demonstrate that measured and MC ion chamber doses agree within 0.6% for the 6X beam and within 2.0% for the 6X FFF beam. A 3D gamma factor analysis demonstrates that for the 6X beam, > 99% of voxels meet the pass criteria (3%/3 mm). For the 6X FFF beam, > 94% of voxels meet this criteria. The TrueBeam accelerator delivering 6X and 6X FFF beams with the HD120 MLC can be modeled in Monte Carlo to provide an independent 3D dose calculation for clinical VMAT plans. This quality assurance tool has been used clinically to verify over 140 6X and 16 6X FFF TrueBeam treatment plans. PACS number: 87.55.K‐ PMID:24892341

Errors introduced by dose scaling for relative dosimetry

PubMed Central

Watanabe, Yoichi; Hayashi, Naoki

2012-01-01

Some dosimeters require a relationship between detector signal and delivered dose. The relationship (characteristic curve or calibration equation) usually depends on the environment under which the dosimeters are manufactured or stored. To compensate for the difference in radiation response among different batches of dosimeters, the measured dose can be scaled by normalizing the measured dose to a specific dose. Such a procedure, often called “relative dosimetry”, allows us to skip the time‐consuming production of a calibration curve for each irradiation. In this study, the magnitudes of errors due to the dose scaling procedure were evaluated by using the characteristic curves of BANG3 polymer gel dosimeter, radiographic EDR2 films, and GAFCHROMIC EBT2 films. Several sets of calibration data were obtained for each type of dosimeters, and a calibration equation of one set of data was used to estimate doses of the other dosimeters from different batches. The scaled doses were then compared with expected doses, which were obtained by using the true calibration equation specific to each batch. In general, the magnitude of errors increased with increasing deviation of the dose scaling factor from unity. Also, the errors strongly depended on the difference in the shape of the true and reference calibration curves. For example, for the BANG3 polymer gel, of which the characteristic curve can be approximated with a linear equation, the error for a batch requiring a dose scaling factor of 0.87 was larger than the errors for other batches requiring smaller magnitudes of dose scaling, or scaling factors of 0.93 or 1.02. The characteristic curves of EDR2 and EBT2 films required nonlinear equations. With those dosimeters, errors larger than 5% were commonly observed in the dose ranges of below 50% and above 150% of the normalization dose. In conclusion, the dose scaling for relative dosimetry introduces large errors in the measured doses when a large dose scaling is applied, and this procedure should be applied with special care. PACS numbers: 87.56.Da, 06.20.Dk, 06.20.fb PMID:22955658

A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage III non-small cell lung cancer.

PubMed

Center, Brian; Petty, William Jeffrey; Ayala, Diandra; Hinson, William H; Lovato, James; Capellari, James; Oaks, Timothy; Miller, Antonius A; Blackstock, Arthur William

2010-01-01

Concurrent radiation and chemotherapy is the standard of care for good performance status patients with stage III non-small cell lung cancer. Locoregional control remains a significant factor relating to poor outcome. Preclinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity. This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy. Patients with histologically confirmed, inoperable stage III non-small cell lung cancer and good performance status (Eastern Cooperative Oncology Group 0-1) were eligible for this study. Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous, weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients. Patients were given a 2-week rest period after the concurrent therapy, during which they received only gefitinib. After the 2-week rest period, patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles. Maintenance gefitinib was continued until disease progression or study completion. Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics: median age, 64 years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk. Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade 3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients, respectively. The overall response rate was 46%, and the median survival for all patients was 21 months. Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity. For further studies, the recommended weekly docetaxel dose for this chemoradiation regimen is 20 mg/m2.

Characterizing proton-activated materials to develop PET-mediated proton range verification markers

NASA Astrophysics Data System (ADS)

Cho, Jongmin; Ibbott, Geoffrey S.; Kerr, Matthew D.; Amos, Richard A.; Stingo, Francesco C.; Marom, Edith M.; Truong, Mylene T.; Palacio, Diana M.; Betancourt, Sonia L.; Erasmus, Jeremy J.; DeGroot, Patricia M.; Carter, Brett W.; Gladish, Gregory W.; Sabloff, Bradley S.; Benveniste, Marcelo F.; Godoy, Myrna C.; Patil, Shekhar; Sorensen, James; Mawlawi, Osama R.

2016-06-01

Conventional proton beam range verification using positron emission tomography (PET) relies on tissue activation alone and therefore requires particle therapy PET whose installation can represent a large financial burden for many centers. Previously, we showed the feasibility of developing patient implantable markers using high proton cross-section materials (18O, Cu, and 68Zn) for in vivo proton range verification using conventional PET scanners. In this technical note, we characterize those materials to test their usability in more clinically relevant conditions. Two phantoms made of low-density balsa wood (~0.1 g cm-3) and beef (~1.0 g cm-3) were embedded with Cu or 68Zn foils of several volumes (10-50 mm3). The metal foils were positioned at several depths in the dose fall-off region, which had been determined from our previous study. The phantoms were then irradiated with different proton doses (1-5 Gy). After irradiation, the phantoms with the embedded foils were moved to a diagnostic PET scanner and imaged. The acquired data were reconstructed with 20-40 min of scan time using various delay times (30-150 min) to determine the maximum contrast-to-noise ratio. The resultant PET/computed tomography (CT) fusion images of the activated foils were then examined and the foils’ PET signal strength/visibility was scored on a 5 point scale by 13 radiologists experienced in nuclear medicine. For both phantoms, the visibility of activated foils increased in proportion to the foil volume, dose, and PET scan time. A linear model was constructed with visibility scores as the response variable and all other factors (marker material, phantom material, dose, and PET scan time) as covariates. Using the linear model, volumes of foils that provided adequate visibility (score 3) were determined for each dose and PET scan time. The foil volumes that were determined will be used as a guideline in developing practical implantable markers.

A phase I and pharmacologic trial of two schedules of the proteasome inhibitor, PS-341 (bortezomib, velcade), in patients with advanced cancer.

PubMed

Dy, Grace K; Thomas, James P; Wilding, George; Bruzek, Laura; Mandrekar, Sumithra; Erlichman, Charles; Alberti, Dona; Binger, Kim; Pitot, Henry C; Alberts, Steven R; Hanson, Lorelei J; Marnocha, Rebecca; Tutsch, Kendra; Kaufmann, Scott H; Adjei, Alex A

2005-05-01

To define the toxicities, pharmacodynamics, and clinical activity of the proteasome inhibitor, PS-341 (bortezomib), in patients with advanced malignancies. Twenty-eight patients (14 male and 14 female) received PS-341 twice weekly for 4 of 6 weeks (schedule I). Because toxicity necessitated dose omissions on this schedule, 16 additional patients (12 male and 4 female) received PS-341 twice weekly for 2 of every 3 weeks (schedule II). A total of 73 courses of treatment was given (median, 2; range, 1-4). Inhibition of 20S proteasome activity in peripheral blood mononuclear cells (PBMC) and accumulation of proteasome-targeted polypeptides in tumor tissue were evaluated as pharmacodynamic markers of PS-341 activity. The most common toxicity was thrombocytopenia, which was dose limiting at 1.7 mg/m2 (schedule I) and 1.6 mg/m2 (schedule II), respectively. Sensory neuropathy was dose-limiting in a patient in schedule I. Grade > or =3 toxicities for schedule I were constipation, fatigue, myalgia, and sensory neuropathy. Grade > or =3 toxicities for schedule II were dehydration resulting from diarrhea, nausea and vomiting, fatigue, hypoglycemia, and hypotension. The maximum tolerated dose was 1.5 mg/m2 for both schedules. Reversible dose-dependent decreases in 20S proteasome activity in PBMCs were observed, with 36% inhibition at 0.5 mg/m2, 52% at 0.9 mg/m2, and 75% at 1.25 mg/m2. Accumulation of proteasome-targeted polypeptides was detected in tumor samples after treatment with PS-341. A patient with multiple myeloma had a partial response. PS-341 given 1.5 mg/m2 twice weekly for 2 of every 3 weeks is well tolerated and should be further studied.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCulloch, M; Cazoulat, G; Polan, D

Purpose: It is well documented that the delivered dose to patients undergoing radiotherapy (RT) is often different from the planned dose due to geometric variability and uncertainties in patient positioning. Recent work suggests that accumulated dose to the GTV is a better predictor of progression compared to the minimum planned dose to the PTV. The purpose of this study is to evaluate if deviations from the planned dose can contributed to tumor progression. Methods: From 2010 to 2014 an in-house Phase II clinical trial of adaptive stereotactic body RT was completed. Of the 90 patients enrolled, 7 patients had amore » local recurrence defined on contrast enhanced CT or MR imaging 3–21 months after completion of RT. Retrospective dose accumulation was performed using a biomechanical model-based deformable image registration algorithm (DIR) to accumulate the dose based on the kV CBCT acquired prior to each fraction for soft tissue alignment of the patient. The DIR algorithm was previously validated for geometric accuracy in the liver (target registration error = 2.0 mm) and dose accumulation in a homogeneous image, similar to a liver CBCT (gamma index = 91%). Following dose accumulation, the minimum dose to 0.5 cc of the GTV was compared between the planned and accumulated dose. Work is ongoing to evaluate the tumor control probability based on the planned and accumulated dose. Results: DIR and dose accumulation was performed on all fractions for 6 patients with local recurrence. The difference in minimum dose to 0.5 cc of the GTV ranged from −0.3–2.3 Gy over 3–5 fractions. One patient had a potentially significant difference in minimum dose of 2.3 Gy. Conclusion: Dose accumulation can reveal tumor underdosage, improving our ability to understand recurrence and tumor progression patterns, and could aid in adaptive re-planning during therapy to correct for this. This work was supported in part by NIH P01CA059827.« less

Initial Report of a Prospective Dosimetric and Clinical Feasibility Trial Demonstrates the Potential of Protons to Increase the Therapeutic Ratio in Breast Cancer Compared With Photons.

PubMed

Bradley, Julie A; Dagan, Roi; Ho, Meng Wei; Rutenberg, Michael; Morris, Christopher G; Li, Zuofeng; Mendenhall, Nancy P

2016-05-01

To compare dosimetric endpoints between proton therapy (PT) and conventional radiation and determine the feasibility of PT for regional nodal irradiation (RNI) in women with breast cancer. From 2012 to 2014, 18 women (stage IIA-IIIB) requiring RNI prospectively enrolled on a pilot study. Median age was 51.8 years (range, 42-73 years). The cohort included breast-conserving therapy (BCT) and mastectomy patients and right- and left-sided cancers. Treatment targets and organs at risk were delineated on computed tomography scans, and PT and conventional plans were developed. Toxicity was prospectively recorded using Common Terminology Criteria for Adverse Events version 4.0. A Wilcoxon signed-rank sum test compared the dose-volume parameters. The primary endpoint was a reduction in cardiac V5. Median follow-up was 20 months (range, 2-31 months). For all patients, the PT plan better met the dosimetric goals and was used for treatment. Proton therapy alone was used for 10 patients (9 postmastectomy, 1 after BCT) and combined proton-photon in 8 (6 BCT, 2 postmastectomy with immediate expander reconstruction). Proton therapy improved coverage of level 2 axilla (P=.0005). Adequate coverage of internal mammary nodes was consistently achieved with PT (median D95, 50.3 Gy; range, 46.6-52.1 Gy) but not with conventional radiation therapy (median D95, 48.2 Gy; range, 40.8-55 Gy; P=.0005). Median cardiac V5 was 0.6% with PT and 16.3% with conventional radiation (P<.0001). Median ipsilateral lung V5 and V20 were improved with PT (median V5 35.3% vs 60.5% [P<.0001]; and median V20, 21.6% vs 35.5% [P<.0001]). Grade 3 dermatitis developed in 4 patients (22%), which was the only grade 3 toxicity. No grade 4+ toxicities developed. Proton therapy for RNI after mastectomy or BCT significantly improves cardiac dose, especially for left-sided patients, and lung V5 and V20 in all patients without excessive acute toxicity. Proton therapy simultaneously improves target coverage for the internal mammary nodes and level 2 axilla, which may positively impact long-term survival in breast cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zelefsky, Michael J., E-mail: zelefskm@mskcc.org; Greco, Carlo; Motzer, Robert

2012-04-01

Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a highmore » single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.« less

Chernobyl doses. Volume 1. Analysis of forest canopy radiation response from multispectral imagery and the relationship to doses. Technical report, 29 July 1987-30 September 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClennan, G.E.; Anno, G.H.; Whicker, F.W.

1994-09-01

This volume of the report Chernobyl Doses presents details of a new, quantitative method for remotely sensing ionizing radiation dose to vegetation. Analysis of Landsat imagery of the area within a few kilometers of the Chernobyl nuclear reactor station provides maps of radiation dose to pine forest canopy resulting from the accident of April 26, 1986. Detection of the first date of significant, persistent deviation from normal of the spectral reflectance signature of pine foliage produces contours of radiation dose in the 20 to 80 Gy range extending up to 4 km from the site of the reactor explosion. Themore » effective duration of exposure for the pine foliage is about 3 weeks. For this exposure time, the LD50 of Pinus sylvestris (Scotch pine) is about 23 Gy. The practical lower dose limit for the remote detection of radiation dose to pine foliage with the Landsat Thematic Mapper is about 5 Gy or 1/4 of the LD50.« less

[Experimental and clinical evaluation latamoxef in newborn and premature infants].

PubMed

Toyonaga, Y; Kurosu, Y; Sugita, M; Kitagawa, M; Hori, M

1983-09-01

Basic and clinical studies of latamoxef (LMOX) were carried out in neonates. In basic study, these neonates consisted of 16 mature babies and 12 premature babies. LMOX was administered at dose of 10 and 20 mg/kg, either as a single intravenous injection or as a 60 minutes intravenous drip infusion. Both the mature babies and the premature babies were divided into 3 subgroups as a function of the number of days after birth (0--3, 4--7 and 8--25 days). A clinical study of LMOX was performed in 12 neonates aged between 0--35 days, consisting 6 males and 6 females. (Purulent meningitis 4 cases, septicemia 1 case, bronchopneumonia 5 cases, pertussis pneumonia 1 case, urinary tract infection 1 case). Serum concentration and urinary excretion 10 mg/kg, one shot intravenous injection In the 3 subgroups of neonates the peak serum concentrations of LMOX were found to range from 14.6 to 28.9 micrograms/ml. Although there was no significant difference, the half-life of the drug became shorter as the age of the neonates increased, these values were 4.46, 3.85 and 3.30 hours, respectively. 10 mg/kg, 60 minutes intravenous drip infusion. As above, the peak LMOX serum concentrations were found to range from 23.7 to 38.9 micrograms/ml, the half-lives of the 3 subgroups were 4.83, 2.48 and 3.01 hours, respectively. And urinary excretions were ranged from 46.0 to 56.5% for 6 hours. 20 mg/kg, one shot intravenous injection The peak serum concentrations were found to range from 31.0--82.5 micrograms/ml, and it was found out 3.29--15.9 micrograms/ml at 8 hours after the injection. There was a tendency for the half-life to be shorter in more mature subjects in 3 subgroups. 20 mg/kg, 60 minutes intravenous drip infusion In the 3 subgroups, the peak concentration was the level existing at the end of the intravenous drip infusion, and that showed a range of 41.8--58.6 micrograms/ml. Half-lives were found out the significant difference to their age, these showed 4.08, 2.31 and 2.52 hours. Cerebrospinal fluid concentrations of LMOX Cerebrospinal fluid concentrations of LMOX were studied in 2 cases at the dose about 50 mg/kg. In 1 case, that's meningitis estimated E. coli organism, the cerebrospinal fluid concentrations of LMOX were found to range from 29.0 to 49.9 micrograms/ml in that acute state. In another case from N. meningitidis, that values were found to range 12.1 to 21.3 micrograms/ml. These cerebrospinal levels were superior value at it's penetration ratio. Clinical studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Vitamin D Replacement in Children, Adolescents and Pregnant Women in the Middle East and North Africa

PubMed Central

Chakhtoura, M; El Ghandour, S; Shawwa, K; Akl, EA; Arabi, A; Mahfoud, Z; Habib, RH; Hoballah, H; El Hajj Fuleihan, G

2017-01-01

Introduction Hypovitaminosis D affects one-third to two-thirds of children and pregnant women from the Middle East and North Africa (MENA) region. Objective To evaluate in infants, children, adolescents and pregnant women, from the MENA region, the effect of supplementation with different vitamin D doses on the change in 25-hydroxyvitamin D [25(OH)D] level reached, and other skeletal and non-skeletal outcomes. Methods This is a systematic review of randomized controlled trials of vitamin D supplementation conducted in the MENA region. We conducted a comprehensive literature search in 7 databases, without language or time restriction, until November 2016. Two reviewers abstracted data from the included studies, independently and in duplicate. We calculated the mean difference (MD) and 95% CI of 25(OH)D level reached when at least 2 studies were eligible in each comparison (low (< 800 IU), intermediate (800–2,000 IU) or high (> 2,000 IU) daily dose of vitamin D, or placebo). We pooled data using RevMan version 5.3. Results We identified a total of 15 eligible trials: one in infants, 4 in children and adolescents and 10 in pregnant women. In children and adolescents, an intermediate vitamin D dose (1,901 IU/d), resulted in a mean difference in 25(OH)D level of 13.5 (95% Confidence Interval (CI) 8.1;18.8) ng/ml, compared to placebo, favoring the intermediate dose (p < 0.001). The proportion of children and adolescents reaching a 25(OH)D level ≥ 20 ng/ml was 74% in the intermediate dose group. In pregnant women, four trials started supplementation at 12–16 weeks of gestation and continued until delivery, and six trials started supplementation at 20–28 weeks gestation and stopped it at delivery. The MD in 25(OH)D level reached was 8.6 (95% CI 5.3–11.9) ng/ml (p <0.001) comparing the high dose (3,662 IU/d) to the intermediate dose (1,836 IU/d), and 12.3 (95% CI 6.4–18.2) ng/ml (p <0.001), comparing the high dose (3,399 IU/d) to the low dose (375 IU/d). Comparing the intermediate (1,832 IU/d) to the low dose (301 IU/d), the MD in 25(OH)D level achieved was 7.8 (95% CI 4.5–10.8) ng/ml (p < 0.001). The proportion of pregnant women reaching a 25(OH)D level ≥ 20 ng/ml was 80–90%, 73% and 27–43% in the high, intermediate, and low dose groups, respectively. The risk of bias in the included studies, for children, adolescents and pregnant women, ranged from low to high. Conclusion In children, adolescents and pregnant women from the MENA, an intermediate vitamin D dose of 1,000–2,000 IU seems necessary to allow for the majority of the population to reach a desirable 25(OH)D level of 20 ng/ml. Further high quality RCTs are required to confirm/refute the beneficial impact of vitamin D supplementation on various clinically important outcomes. PMID:28403940

Dose-mass inverse optimization for minimally moving thoracic lesions

NASA Astrophysics Data System (ADS)

Mihaylov, I. B.; Moros, E. G.

2015-05-01

In the past decade, several different radiotherapy treatment plan evaluation and optimization schemes have been proposed as viable approaches, aiming for dose escalation or an increase of healthy tissue sparing. In particular, it has been argued that dose-mass plan evaluation and treatment plan optimization might be viable alternatives to the standard of care, which is realized through dose-volume evaluation and optimization. The purpose of this investigation is to apply dose-mass optimization to a cohort of lung cancer patients and compare the achievable healthy tissue sparing to that one achievable through dose-volume optimization. Fourteen non-small cell lung cancer (NSCLC) patient plans were studied retrospectively. The range of tumor motion was less than 0.5 cm and motion management in the treatment planning process was not considered. For each case, dose-volume (DV)-based and dose-mass (DM)-based optimization was performed. Nine-field step-and-shoot IMRT was used, with all of the optimization parameters kept the same between DV and DM optimizations. Commonly used dosimetric indices (DIs) such as dose to 1% the spinal cord volume, dose to 50% of the esophageal volume, and doses to 20 and 30% of healthy lung volumes were used for cross-comparison. Similarly, mass-based indices (MIs), such as doses to 20 and 30% of healthy lung masses, 1% of spinal cord mass, and 33% of heart mass, were also tallied. Statistical equivalence tests were performed to quantify the findings for the entire patient cohort. Both DV and DM plans for each case were normalized such that 95% of the planning target volume received the prescribed dose. DM optimization resulted in more organs at risk (OAR) sparing than DV optimization. The average sparing of cord, heart, and esophagus was 23, 4, and 6%, respectively. For the majority of the DIs, DM optimization resulted in lower lung doses. On average, the doses to 20 and 30% of healthy lung were lower by approximately 3 and 4%, whereas lung volumes receiving 2000 and 3000 cGy were lower by 3 and 2%, respectively. The behavior of MIs was very similar. The statistical analyses of the results again indicated better healthy anatomical structure sparing with DM optimization. The presented findings indicate that dose-mass-based optimization results in statistically significant OAR sparing as compared to dose-volume-based optimization for NSCLC. However, the sparing is case-dependent and it is not observed for all tallied dosimetric endpoints.

SU-E-T-553: Monte Carlo Calculation of Proton Bragg Peak Displacements in the Presence of Al2O3:C Dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, L; Yang, F

2015-06-15

Purpose: The application of optically stimulated luminescence dosimeters (OSLDs) may be extended to clinical investigations verifying irradiated doses in small animal models. In proton beams, the accurate positioning of the Bragg peak is essential for tumor targeting. The purpose of this study was to estimate the displacement of a pristine Bragg peak when an Al2O3:C nanodot (Landauer, Inc.) is placed on the surface of a water phantom and to evaluate corresponding changes in dose. Methods: Clinical proton pencil beam simulations were carried out with using TOPAS, a Monte Carlo platform layered on top of GEANT4. Point-shaped beams with no energymore » spread were modeled for energies 100MV, 150MV, 200MV, and 250MV. Dose scoring for 100,000 particle histories was conducted within a water phantom (20cm × 20cm irradiated area, 40cm depth) with its surface placed 214.5cm away from the source. The modeled nanodot had a 4mm radius and 0.2mm thickness. Results: A comparative analysis of Monte Carlo depth dose profiles modeled for these proton pencil beams did not demonstrate an energy dependent in the Bragg peak shift. The shifts in Bragg Peak depth for water phantoms modeled with a nanodot on the phantom surface ranged between 2.7 to 3.2 mm. In all cases, the Bragg Peaks were shifted closer to the irradiation source. The peak dose in phantoms with an OSLD remained unchanged with percent dose differences less than 0.55% when compared to phantom doses without the nanodot. Conclusion: Monte Carlo calculations show that the presence of OSLD nanodots in proton beam therapy will not change the position of a pristine Bragg Peak by more than 3 mm. Although the 3.0 mm shift will not have a detrimental effect in patients receiving proton therapy, this effect may not be negligible in dose verification measurements for mouse models at lower proton beam energies.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medina, L; Adrada, A; Filipuzzi, M

Purpose: The purpose of this paper is to characterize EBT3 using two types of scanner, analyzing the factors of influence of each dosimetry system. Methods: The film used in this study was GAFCHROMIC EBT3, the films were exposed at a dose range between 0Gy a 9Gy in a solid water phantom, SSD=100cm, 5cm depth and perpendicularly to the 6MV photon beam generated by a Novalis TX linear accelerator equipped with an HDMLC. A Farmer type ion chamber TN30013 (PTW) was used to determine the dose delivered to the film. The films were digitized with a scanner EPSON expression 10000XL andmore » the VIDAR DosimetryPro Adventage RED. Software RIT113v6.1 was used for construction of the calibration curve and analysis. The film characteristics investigated were: response at different dose levels, sensitivity to orientation and side and resolution through the results of the spatial response function by analyzing a step pattern. Additionally, 20 IMRT treatment fields were measured with both scanner and compared with calculated dose using gamma index analysis (3%-3mm). Results: The OD obtained for dose level 2Gy in the orientation portrait of the film on the scanner EPSON is (0,222±0,19) and for Vidar RED (0,252±0,10) and landscape is for EPSON (0,211±0,25) and for Vidar RED (0,250±0,11) . The orientation dependence with respect to film side is about 0,09% for EPSON and about 0.03% for VIDAR. The spatial response function increase in response to the Gaussian function FWHM EPSON scanner (0.18mm) compared with VIDAR scanner function (less than 0.06mm) was observed. We analyzed 20 total plan dose distributions the number of pixels with gamma>1 (3%-3mm) was 0.7%±1.2 [0.1%; 2.82%] for EBT3-VIDAR y 2%±2.9 [0.2%; 3.5%] for EBT3-EPSON. Conclusion: VIDAR scanner shows better sensitivity. EBT3 film shows a different response between portrait and landscape orientation. Step pattern is better reproduce by VIDAR scanner.« less

In vivo dosimetry with radiochromic films in low-voltage intraoperative radiotherapy of the breast.

PubMed

Avanzo, M; Rink, A; Dassie, A; Massarut, S; Roncadin, M; Borsatti, E; Capra, E

2012-05-01

EBT2 radiochromic films were studied and used for in vivo dosimetry in targeted intraoperative radiotherapy (TARGIT), a technique in which the Intrabeam system (Carl Zeiss, Oberkochen, Germany) is used to perform intraoperative partial breast irradiation with x-rays of 50 kV(p). The energy of the radiation emitted by the Intrabeam with the different spherical applicators, under 1 and 2 cm of solid water, and under the tungsten impregnated rubber used for shielding of the heart in TARGIT of the breast, was characterized with measurements of half-value layer (HVL). The stability of response of EBT2 was verified inside this range of energies. EBT2 films were calibrated using the red and green channels of the absorption spectrum in the 0-20 Gy dose range delivered by the Intrabeam x-rays. The dependence of film response on temperature during irradiation was measured. For in vivo dosimetry, pieces of radiochromic films wrapped in sterile envelopes were inserted after breast conserving surgery and before TARGIT into the excision cavity, on the skin and on the shielded pectoralis fascia for treatments of the left breast. HVLs of the Intrabeam in TARGIT of the breast correspond to effective energies of 20.7-36.3 keV. The response of EBT2 was constant inside this range of energies. We measured the dose to the target tissue and to organs at risk in 23 patients and obtained an average dose of 13.52 ± 1.21 Gy to the target tissue. Dose to the skin in close proximity to the applicator was 2.22 ± 0.97 Gy, 0.29 ± 0.17 Gy at 5-10 cm from the applicator, and 0.08 ± 0.07 Gy at more than 10 cm from the applicator. Dose to the pectoral muscle for left breast treatment was 0.57 ± 0.23 Gy. Our results show that EBT2 films are accurate at the beam energies, dose range, and irradiation temperature found in TARGIT and that in vivo dosimetry in TARGIT with EBT2 films wrapped in sterile envelopes is a feasible procedure. Measured dose to the organs at risk indicates that the technique is safe from side effects to the skin and the heart.

In vivo dosimetry with radiochromic films in low-voltage intraoperative radiotherapy of the breast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avanzo, M.; Rink, A.; Dassie, A.

Purpose: EBT2 radiochromic films were studied and used for in vivo dosimetry in targeted intraoperative radiotherapy (TARGIT), a technique in which the Intrabeam system (Carl Zeiss, Oberkochen, Germany) is used to perform intraoperative partial breast irradiation with x-rays of 50 kV{sub p}. Methods: The energy of the radiation emitted by the Intrabeam with the different spherical applicators, under 1 and 2 cm of solid water, and under the tungsten impregnated rubber used for shielding of the heart in TARGIT of the breast, was characterized with measurements of half-value layer (HVL). The stability of response of EBT2 was verified inside thismore » range of energies. EBT2 films were calibrated using the red and green channels of the absorption spectrum in the 0-20 Gy dose range delivered by the Intrabeam x-rays. The dependence of film response on temperature during irradiation was measured. For in vivo dosimetry, pieces of radiochromic films wrapped in sterile envelopes were inserted after breast conserving surgery and before TARGIT into the excision cavity, on the skin and on the shielded pectoralis fascia for treatments of the left breast. Results: HVLs of the Intrabeam in TARGIT of the breast correspond to effective energies of 20.7-36.3 keV. The response of EBT2 was constant inside this range of energies. We measured the dose to the target tissue and to organs at risk in 23 patients and obtained an average dose of 13.52 {+-} 1.21 Gy to the target tissue. Dose to the skin in close proximity to the applicator was 2.22 {+-} 0.97 Gy, 0.29 {+-} 0.17 Gy at 5-10 cm from the applicator, and 0.08 {+-} 0.07 Gy at more than 10 cm from the applicator. Dose to the pectoral muscle for left breast treatment was 0.57 {+-} 0.23 Gy. Conclusions: Our results show that EBT2 films are accurate at the beam energies, dose range, and irradiation temperature found in TARGIT and that in vivo dosimetry in TARGIT with EBT2 films wrapped in sterile envelopes is a feasible procedure. Measured dose to the organs at risk indicates that the technique is safe from side effects to the skin and the heart.« less

The Impact of CB2 Receptor Ligands on the MK-801-Induced Hyperactivity in Mice.

PubMed

Kruk-Slomka, Marta; Banaszkiewicz, Izabela; Biala, Grazyna

2017-04-01

It has been known that there is a relationship between cannabis use and schizophrenia-related symptoms; however, it can be a subject of controversy. The involvement of CB1 receptor ligands in the schizophrenia has already been revealed and confirmed. However, there is still lack of information concerning the role of CB2 receptors in the psychosis-like effects in mice and the further studies are needed.The aim of the present research was to study the role of the CB2 receptor ligands in the symptoms typical for schizophrenia. We provoked hyperlocomotion in mice which is analogous to positive psychosis-like effects in humans, by an acute administration of a NMDA receptor antagonist, MK-801 (0.3 and 0.6 mg/kg), a pharmacological model of schizophrenia. An acute administration of MK-801 induced the increase in locomotor activity (hyperactivity) in rodents, measured in actimeters.We revealed that an acute injection of CB2 receptor agonist JWH 133 at the dose range (0.05-1.0 mg/kg) and CB2 receptor antagonist, AM 630 at the dose range (0.1-1.0 mg/kg) decreased locomotion of mice. An acute injection of JWH 133 (2.0 mg/kg) and AM 630 (2.0 mg/kg) had no statistical significant influence on the locomotor activity of mice. However, an acute injection of both CB2 receptor ligands (agonist and antagonist), JWH 133, at the non-effective dose of 2.0 mg/kg and AM 630 at the non-effective dose of 2.0 mg/kg, potentiated the MK-801-induced hyperactivity.The present findings have confirmed that endocannabinoid system, not only via CB1, but also via CB2 receptors, may be involved in the schizophrenia-like responses, including hyperlocomotion in mice.

Radiosurgery for hemangioblastoma: results of a multiinstitutional experience.

PubMed

Patrice, S J; Sneed, P K; Flickinger, J C; Shrieve, D C; Pollock, B E; Alexander, E; Larson, D A; Kondziolka, D S; Gutin, P H; Wara, W M; McDermott, M W; Lunsford, L D; Loeffler, J S

1996-06-01

Between June 1988 and June 1994. 38 hemangioblastomas were treated with stereotactic radiosurgery (SR) at three SR centers to evaluate the efficacy and potential toxicity of this therapeutic modality as an adjuvant or alternative treatment to surgical resection. SR was performed using either a 201-cobalt source unit or a dedicated SR linear accelerator. Of the 18 primary tumors treated, 16 had no prior history of surgical resection and were treated definitively with SR and two primary lesions were subtotally resected and subsequently treated with SR. Twenty lesions were treated with SR after prior surgical failure (17 tumors) or failure after prior surgery and conventional radiotherapy (three tumors). Eight patients were treated with SR for multifocal disease (total, 24 known tumors). SR tumor volumes measured 0.05 to 12 cc (median: 0.97 cc). Minimum tumor doses ranged from 12 to 20 Gy (median: 15.5 Gy). Median follow-up from the time of SR was 24.5 months (range: 6-77 months). The 2-year actuarial over-all survival was 88 +/- 15% (95% confidence interval). Two-year actuarial freedom from progression was 86 +/- 12% (95% confidence interval). The median tumor volume of the lesions that failed to be controlled by SR was 7.85 cc (range: 3.20-10.53 cc) compared to 0.67 cc (range: 0.05-12 cc) for controlled lesions (p - 0.0023). The lesions that failed to be controlled by SR received a median minimum tumor dose of 14 Gy (range: 13-17 Gy) compared to 16 Gy (range: 12-20 Gy) for controlled lesions (p = 0.0239). Seventy-eight percent of the surviving patients remained neurologically stable or clinically improved. There were no significant permanent complications directly attributable to SR. This report documents the largest experience in the literature of the use of SR in the treatment of hemangioblastoma. We conclude that SR: (a) controls the majority of primary and recurrent hemangioblastomas; (b) offers the ability to treat multiple lesions in a single treatment session, which is particularly important for patients with Von Hippel-Lindau Syndrome; and that (c) better control rates are associated with higher doses and smaller tumor volumes.

Daily Rifapentine for Treatment of Pulmonary Tuberculosis. A Randomized, Dose-Ranging Trial

PubMed Central

Savic, Radojka M.; Goldberg, Stefan; Stout, Jason E.; Schluger, Neil; Muzanyi, Grace; Johnson, John L.; Nahid, Payam; Hecker, Emily J.; Heilig, Charles M.; Bozeman, Lorna; Feng, Pei-Jean I.; Moro, Ruth N.; MacKenzie, William; Dooley, Kelly E.; Nuermberger, Eric L.; Vernon, Andrew; Weiner, Marc

2015-01-01

Rationale: Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. Objectives: We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. Methods: Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. Measurements and Main Results: A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration–time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). Conclusions: Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629). PMID:25489785

Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial.

PubMed

Dorman, Susan E; Savic, Radojka M; Goldberg, Stefan; Stout, Jason E; Schluger, Neil; Muzanyi, Grace; Johnson, John L; Nahid, Payam; Hecker, Emily J; Heilig, Charles M; Bozeman, Lorna; Feng, Pei-Jean I; Moro, Ruth N; MacKenzie, William; Dooley, Kelly E; Nuermberger, Eric L; Vernon, Andrew; Weiner, Marc

2015-02-01

Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).

Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors.

PubMed

Gladman, Dafna; Rigby, William; Azevedo, Valderilio F; Behrens, Frank; Blanco, Ricardo; Kaszuba, Andrzej; Kudlacz, Elizabeth; Wang, Cunshan; Menon, Sujatha; Hendrikx, Thijs; Kanik, Keith S

2017-10-19

Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors. In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis. At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib. In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).

The importance of vitamin C for hydroxylation of vitamin D3 to 1,25(OH)2D3 in man.

PubMed

Cantatore, F P; Loperfido, M C; Magli, D M; Mancini, L; Carrozzo, M

1991-06-01

The effects of vitamin C on 1,25(OH)2D3 synthesis in humans were evaluated; the study included 20 females. They were divided into 2 groups. The first of the 10 subjects (age range 55-71) received ascorbic acid at a dose of 150 mg/die i.v. for 10 days; the second 10 subjects (age range 55-69) received a placebo i.v. for 10 days. In a later study (after a 30-day washout) the same two groups were tested for the second time with ascorbic acid at a dose of 1,000 mg/die i.v. for 10 days and placebo i.v. for 10 days. Serum calcium and phosphorus, serum Ca++, serum proteins, blood and urinary pH, serum 25(OH)D3 and 1,25(OH)2D3, serum PTH, urinary hydroxyprolin were tested before and after the treatments. In the first study a significant increase in serum 1,25(OH)2D3 was observed after ascorbic acid while no significant variation was observed for the other parameters. In the second study, a significant increase in serum Ca++ and a significant decrease in serum 1,25(OH)2D3 were observed after ascorbic acid while no significant variation was observed for the other parameters. The authors conclude that ascorbic acid promotes 1,25(OH)2D3 synthesis at a paraphysiologic dose (150 mg/die) in humans but this synthesis is inhibited at higher doses (1,000 mg/die). The latter effect by Ca++ or by an effect of ascorbate on 1 alpha-hydroxylase enzyme could be mediated.

SU-G-BRA-15: Dosimetric Evaluation of Dynamic Tumor Tracking Radiation Therapy Using Digital Phantom: A Study On Margin and Desired Accuracy of Tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uchida, T; Osanai, M; Homma, N

2016-06-15

Purpose: Dynamic tumor tracking radiation therapy can potentially reduce internal margin without prolongation of irradiation time. However, dynamic tumor tracking technique requires an extra margin (tracking margin, TM) for the uncertainty of tumor localization, prediction, and beam repositioning. The purpose of this study was to evaluate a dosimetric impact caused by TM. Methods: We used 4D XCAT to create 9 digital phantom datasets of different tumor size and motion range: tumor diameter TD=(1, 3, 5) cm and motion range MR=(1, 2, 3) cm. For each dataset, respiratory gating (30%–70% phase) and tumor tracking treatment plans were created using 8-field 3D-CRTmore » by 4D dose calculation implemented in RayStation. The dose constraint was based on RTOG0618. For the tracking plan, TMs of (0, 2.5, 5) mm were considered by surrounding a normal setup margin: SM=5 mm. We calculated V20 of normal lung to evaluate the dosimetric impact for each case, and estimated an equivalent TM that affects the same impact on V20 obtained by the gated plan. Results: The equivalent TMs for (TD=1 cm, MR=2 cm), (TD=1 cm, MR=3 cm), (TD=5 cm, MR=2 cm), and (TD=5 cm, MR=3 cm) were estimated as 1.47 mm, 3.95 mm, 1.04 mm, and 2.13 mm, respectively. The larger the tumor size, the equivalent TM became smaller. On the other hand, the larger the motion range, the equivalent TM was found to be increased. Conclusion: Our results showed the equivalent TM changes depending on tumor size and motion range. The tracking plan with TM less than the equivalent TM achieves a dosimetric impact better than the gated plan in less treatment time. This study was partially supported by JSPS Kakenhi and Varian Medical Systems.« less

Optimization of leaf margins for lung stereotactic body radiotherapy using a flattening filter-free beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wakai, Nobuhide, E-mail: wakai@naramed-u.ac.jp; Sumida, Iori; Otani, Yuki

Purpose: The authors sought to determine the optimal collimator leaf margins which minimize normal tissue dose while achieving high conformity and to evaluate differences between the use of a flattening filter-free (FFF) beam and a flattening-filtered (FF) beam. Methods: Sixteen lung cancer patients scheduled for stereotactic body radiotherapy underwent treatment planning for a 7 MV FFF and a 6 MV FF beams to the planning target volume (PTV) with a range of leaf margins (−3 to 3 mm). Forty grays per four fractions were prescribed as a PTV D95. For PTV, the heterogeneity index (HI), conformity index, modified gradient indexmore » (GI), defined as the 50% isodose volume divided by target volume, maximum dose (Dmax), and mean dose (Dmean) were calculated. Mean lung dose (MLD), V20 Gy, and V5 Gy for the lung (defined as the volumes of lung receiving at least 20 and 5 Gy), mean heart dose, and Dmax to the spinal cord were measured as doses to organs at risk (OARs). Paired t-tests were used for statistical analysis. Results: HI was inversely related to changes in leaf margin. Conformity index and modified GI initially decreased as leaf margin width increased. After reaching a minimum, the two values then increased as leaf margin increased (“V” shape). The optimal leaf margins for conformity index and modified GI were −1.1 ± 0.3 mm (mean ± 1 SD) and −0.2 ± 0.9 mm, respectively, for 7 MV FFF compared to −1.0 ± 0.4 and −0.3 ± 0.9 mm, respectively, for 6 MV FF. Dmax and Dmean for 7 MV FFF were higher than those for 6 MV FF by 3.6% and 1.7%, respectively. There was a positive correlation between the ratios of HI, Dmax, and Dmean for 7 MV FFF to those for 6 MV FF and PTV size (R = 0.767, 0.809, and 0.643, respectively). The differences in MLD, V20 Gy, and V5 Gy for lung between FFF and FF beams were negligible. The optimal leaf margins for MLD, V20 Gy, and V5 Gy for lung were −0.9 ± 0.6, −1.1 ± 0.8, and −2.1 ± 1.2 mm, respectively, for 7 MV FFF compared to −0.9 ± 0.6, −1.1 ± 0.8, and −2.2 ± 1.3 mm, respectively, for 6 MV FF. With the heart inside the radiation field, the mean heart dose showed a V-shaped relationship with leaf margins. The optimal leaf margins were −1.0 ± 0.6 mm for both beams. Dmax to the spinal cord showed no clear trend for changes in leaf margin. Conclusions: The differences in doses to OARs between FFF and FF beams were negligible. Conformity index, modified GI, MLD, lung V20 Gy, lung V5 Gy, and mean heart dose showed a V-shaped relationship with leaf margins. There were no significant differences in optimal leaf margins to minimize these parameters between both FFF and FF beams. The authors’ results suggest that a leaf margin of −1 mm achieves high conformity and minimizes doses to OARs for both FFF and FF beams.« less

Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions.

PubMed

Elmore, E; Lao, X-Y; Kapadia, R; Redpath, J L

2009-06-01

Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has been examined. The data indicate a threshold-type dose-response curve with no increase in transformation frequency until doses above 20 cGy. At doses <10 cGy, not all exposed cells receive a direct traversal of an iron-ion track core, but all exposed cells receive up to several mGy of low-LET radiation associated with the delta-ray penumbra. It is proposed that the threshold-type response seen is a consequence of an adaptive response associated with the delta-ray exposure. For comparison purposes, the dose response for (137)Cs gamma rays over the same dose range was examined using the same experimental procedure. As we have shown previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron ions were 1.5 to 1.7 times more biologically effective than the gamma radiation over the dose range examined.

Eye lens dosimetry and the study on radiation cataract in interventional cardiologists.

PubMed

Matsubara, Kosuke; Lertsuwunseri, Vorarit; Srimahachota, Suphot; Krisanachinda, Anchali; Tulvatana, Wasee; Khambhiphant, Bharkbhum; Sudchai, Waraporn; Rehani, Madan

2017-12-01

To determine the eye lens dose of the Interventional Cardiology (IC) personnel using optically stimulated luminescent dosimeter (OSLD) and the prevalence and risk of radiation - associated lens opacities in Thailand. 48 IC staff, with age- and sex- matches 37 unexposed controls obtained eye examines. Posterior lens change was graded using a modified Merriam-Focht technique by two independent ophthalmologists. Occupational exposure (mSv) was measured in 42 IC staff, using 2 OSLD badges place at inside lead apron and at collar. Annual eye lens doses (mSv) were also measured using 4 nanoDots OSL placed outside and inside lead glass eyewear. The prevalence of radiation-associated posterior lens opacities was 28.6% (2/7) for IC, 19.5% (8/41) for nurses, and 2.7% (1/37) for controls. The average and range of annual whole body effective dose, Hp(10), equivalent dose at skin of the neck, Hp(0.07) and equivalent dose at eye lens, Hp(3) were 0.80 (0.05-6.79), 5.88 (0.14-35.28), and 5.73 (0.14-33.20) mSv respectively. The annual average and range of eye lens dose using nano Dots OSL showed the outside lead glass eyewear on left and right sides as 8.06 (0.17-32.45), 3.55(0.06-8.04) mSv and inside left and right sides as 3.91(0.05-14.26) and 2.44(0.06-6.24) mSv respectively. Eye lens doses measured by OSLD badges and nano Dot dosimeter as Hp(10), Hp(0.07) and Hp(3). The eyes of the IC personnel were examined annually by two ophthalmologists for the prevalence of cataract induced by radiation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Dose-Reduced Busulfan, Cyclophosphamide, and Autologous Stem Cell Transplantation for Human Immunodeficiency Virus–Associated Lymphoma: AIDS Malignancy Consortium Study 020

PubMed Central

Spitzer, Thomas R.; Ambinder, Richard F.; Lee, Jeannette Y.; Kaplan, Lawrence D.; Wachsman, William; Straus, David J.; Aboulafia, David M.; Scadden, David T.

2013-01-01

Intensive chemotherapy for human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) has resulted in durable remissions in a substantial proportion of patients. High-dose chemotherapy and autologous stem cell transplantation (AuSCT), moreover, has resulted in sustained complete remissions in selected patients with recurrent chemosensitive disease. Based on a favorable experience with dose-reduced high-dose busulfan, cyclophosphamide, and AuSCT for older patients with non-HIV–associated aggressive lymphomas, an AIDS Malignancy Consortium multicenter trial was undertaken using the same dose-reduced busulfan and cyclophosphamide preparative regimen with AuSCT for recurrent HIV-associated NHL and HL. Of the 27 patients in the study, 20 received an AuSCT. The median time to achievement of an absolute neutrophil count (ANC) of ≥ 0.5 × 109/L was 11 days (range, 9-16 days). The median time to achievement of an unsupported platelet count of ≥ 20 × 109/L was 13 days (range, 6-57 days). One patient died on day +33 posttransplantation from hepatic veno-occlusive disease (VOD) and multiorgan failure. No other fatal regimen-related toxicity occurred. Ten of 19 patients (53%) were in complete remission at the time of their day +100 post-AuSCT evaluation. Of the 20 patients, 10 were alive and event-free at a median of 23 weeks post-AuSCT. Median overall survival (OS) was not reached by 13 of the 20 patients alive at the time of last follow-up. This multi-institutional trial demonstrates that a regimen of dose-reduced high-dose busulfan, cyclophosphamide, and AuSCT is well tolerated and is associated with favorable disease-free survival (DFS) and OS probabilities for selected patients with HIV-associated NHL and HL. PMID:18158962

Distribution of radionuclides in Dardanelle Reservoir sediments.

PubMed

Forgy, J R; Epperson, C E; Swindle, D L

1984-02-01

Natural and reactor-discharged gamma-ray emitting radionuclides were measured in Dardanelle Reservoir surface sediments taken near the Arkansas Nuclear One Power Plant site. Samples represented several water depths and particle sizes, at 33 locations, in a field survey conducted in early September 1980. Radionuclide contents of dry sediments ranged as follows: natural radioactivity (40K as well as uranium and thorium decay products) 661-1210 Bq/kg; and reactor discharged radioactivity (137Cs, 134Cs, 60Co,, 58Co, 54Mn), no detectable activity to 237 Bq/kg. In general, radionuclide contents were positively correlated with decreasing sediment particle size. The average external whole-body and skin doses from all measurable reactor-discharged radionuclides were calculated according to the mathematical formula for determining external dose from sediment given by the U.S. Nuclear Regulatory Commission (NRC). Inside the discharge embayment near the reactor discharge canal, the doses were 1.7 X 10(-3) mSv/yr to the whole body and 2.0 X 10(-3) mSv/yr to the skin. Outside this area, the doses were 0.15 X 10(-3) and 0.18 X 10(-3) mSv/yr to the whole body and skin, respectively.

Peripheral organ doses from radiotherapy for heterotopic ossification of non-hip joints: is there a risk for radiation-induced malignancies?

PubMed

Berris, Theocharis; Mazonakis, Michalis; Kachris, Stefanos; Damilakis, John

2014-05-01

Radiotherapy, used for heterotopic ossification (HO) management, may increase radiation risk to patients. This study aimed to determine the peripheral dose to radiosensitive organs and the associated cancer risks due to radiotherapy of HO in common non-hip joints. A Monte Carlo model of a medical linear accelerator combined with a mathematical phantom representing an average adult patient were employed to simulate radiotherapy for HO with standard AP and PA fields in the regions of shoulder, elbow and knee. Radiation dose to all out-of-field radiosensitive organs defined by the International Commission on Radiological Protection was calculated. Cancer induction risk was estimated using organ-specific risk coefficients. Organ dose change with increased field dimensions was also evaluated. Radiation therapy for HO with a 7 Gy target dose in the sites of shoulder, elbow and knee, resulted in the following equivalent organ dose ranges of 0.85-62 mSv, 0.28-1.6 mSv and 0.04-1.6 mSv, respectively. Respective ranges for cancer risk were 0-5.1, 0-0.6 and 0-1.3 cases per 10(4) persons. Increasing the field size caused an average increase of peripheral doses by 15-20%. Individual organ dose increase depends upon the primary treatment site and the distance between organ of interest and treatment volume. Relatively increased risks of more than 1 case per 10,000 patients were found for skin, breast and thyroid malignancies after treatment in the region of shoulder and for skin cancer following elbow irradiation. The estimated risk for inducing any other malignant disease ranges from negligible to low. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

RNA Nanoparticles Derived from Three-Way Junction of Phi29 Motor pRNA Are Resistant to I-125 and Cs-131 Radiation

PubMed Central

Li, Hui; Rychahou, Piotr G.; Cui, Zheng; Pi, Fengmei; Evers, B. Mark; Shu, Dan

2015-01-01

Radiation reagents that specifically target tumors are in high demand for the treatment of cancer. The emerging field of RNA nanotechnology might provide new opportunities for targeted radiation therapy. This study investigates whether chemically modified RNA nanoparticles derived from the packaging RNA (pRNA) three-way junction (3WJ) of phi29 DNA-packaging motor are resistant to potent I-125 and Cs-131 radiation, which is a prerequisite for utilizing these RNA nanoparticles as carriers for targeted radiation therapy. pRNA 3WJ nanoparticles were constructed and characterized, and the stability of these nanoparticles under I-125 and Cs-131 irradiation with clinically relevant doses was examined. RNA nanoparticles derived from the pRNA 3WJ targeted tumors specifically and they were stable under irradiation of I-125 and Cs-131 with clinically relevant doses ranging from 1 to 90 Gy over a significantly long time up to 20 days, while control plasmid DNA was damaged at 20 Gy or higher. PMID:26017686

Rituximab in highly sensitized kidney transplant recipients.

PubMed

Munoz, A S; Rioveros, A A; Cabanayan-Casasola, C B; Danguilan, R A; Ona, E T

2008-09-01

Rituximab, an anti-CD20 monoclonal antibody therapy, depletes B cells and suppresses antibody production. This study sought to describe the efficacy and safety of rituximab among seven highly sensitized kidney transplant patients. A highly sensitized patient was defined as panel-reactive antibody (PRA) >30%, more than three pregnancies, or history of positive tissue crossmatch. Demographics, immunological risk profile, and immunosuppression were collected on all highly sensitized patients transplanted from March to July 2007 and given rituximab. We noted graft function as well as clinical events posttransplantation. The seven patients included in the study showed a mean age of 39 years (range = 17-60) and a mean follow-up of 3 months (range = 1.5-5). Their average PRA was 62% with mean HLA mismatches of three. Five patients (71%) were retransplantations; one had a history of a positive crossmatch, and two had multiple pregnancies. Two had donor-specific antibody, but negative tissue crossmatches. All had living donors. Six patients received a single dose of rituximab (375 mg/m2) 1 day prior to transplantation and one received two doses after 19 sessions of plasmapheresis. All were given tacrolimus, mycophenolate, and steroids combined with induction therapy using 30 mg alemtuzumab in 33%; two doses of 20 mg basiliximab in 33%; and seven doses of 1 mg/kg/dose of daclizumab in 14%. Mean shown creatinine levels were 1.1 and 1.2 mg/dL at 1 and 6 months posttransplantation. Two recipients experienced acute humoral rejections within 1 month after transplantation. Both were given steroid pulsing, one of whom was steroid-resistant necessitating alemtuzumab therapy and plasmapheresis. Graft function of both improved with creatinine values of 1.3 mg/dL on discharge. No episodes of infection were noted. Rituximab can be safely administered and may be effective to improve outcomes among highly sensitized kidney transplant patients.

Optimizing Radiation Doses for Computed Tomography Across Institutions: Dose Auditing and Best Practices.

PubMed

Demb, Joshua; Chu, Philip; Nelson, Thomas; Hall, David; Seibert, Anthony; Lamba, Ramit; Boone, John; Krishnam, Mayil; Cagnon, Christopher; Bostani, Maryam; Gould, Robert; Miglioretti, Diana; Smith-Bindman, Rebecca

2017-06-01

Radiation doses for computed tomography (CT) vary substantially across institutions. To assess the impact of institutional-level audit and collaborative efforts to share best practices on CT radiation doses across 5 University of California (UC) medical centers. In this before/after interventional study, we prospectively collected radiation dose metrics on all diagnostic CT examinations performed between October 1, 2013, and December 31, 2014, at 5 medical centers. Using data from January to March (baseline), we created audit reports detailing the distribution of radiation dose metrics for chest, abdomen, and head CT scans. In April, we shared reports with the medical centers and invited radiology professionals from the centers to a 1.5-day in-person meeting to review reports and share best practices. We calculated changes in mean effective dose 12 weeks before and after the audits and meeting, excluding a 12-week implementation period when medical centers could make changes. We compared proportions of examinations exceeding previously published benchmarks at baseline and following the audit and meeting, and calculated changes in proportion of examinations exceeding benchmarks. Of 158 274 diagnostic CT scans performed in the study period, 29 594 CT scans were performed in the 3 months before and 32 839 CT scans were performed 12 to 24 weeks after the audit and meeting. Reductions in mean effective dose were considerable for chest and abdomen. Mean effective dose for chest CT decreased from 13.2 to 10.7 mSv (18.9% reduction; 95% CI, 18.0%-19.8%). Reductions at individual medical centers ranged from 3.8% to 23.5%. The mean effective dose for abdominal CT decreased from 20.0 to 15.0 mSv (25.0% reduction; 95% CI, 24.3%-25.8%). Reductions at individual medical centers ranged from 10.8% to 34.7%. The number of CT scans that had an effective dose measurement that exceeded benchmarks was reduced considerably by 48% and 54% for chest and abdomen, respectively. After the audit and meeting, head CT doses varied less, although some institutions increased and some decreased mean head CT doses and the proportion above benchmarks. Reviewing institutional doses and sharing dose-optimization best practices resulted in lower radiation doses for chest and abdominal CT and more consistent doses for head CT.

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced non-small cell lung cancer.

PubMed

Wu, Chen-Ta; Motegi, Atsushi; Motegi, Kana; Hotta, Kenji; Kohno, Ryosuke; Tachibana, Hidenobu; Kumagai, Motoki; Nakamura, Naoki; Hojo, Hidehiro; Niho, Seiji; Goto, Koichi; Akimoto, Tetsuo

2016-08-10

To assess the feasibility of proton beam therapy for the patients with locally advanced non-small lung cancer. The dosimetry was analyzed retrospectively to calculate the doses to organs at risk, such as the lung, heart, esophagus and spinal cord. A dosimetric comparison between proton beam therapy and dummy photon radiotherapy (three-dimensional conformal radiotherapy) plans was performed. Dummy intensity-modulated radiotherapy plans were also generated for the patients for whom curative three-dimensional conformal radiotherapy plans could not be generated. Overall, 33 patients with stage III non-small cell lung cancer were treated with proton beam therapy between December 2011 and August 2014. The median age of the eligible patients was 67 years (range: 44-87 years). All the patients were treated with chemotherapy consisting of cisplatin/vinorelbine or carboplatin. The median prescribed dose was 60 GyE (range: 60-66 GyE). The mean normal lung V20 GyE was 23.6% (range: 14.9-32%), and the mean normal lung dose was 11.9 GyE (range: 6.0-19 GyE). The mean esophageal V50 GyE was 25.5% (range: 0.01-63.6%), the mean heart V40 GyE was 13.4% (range: 1.4-29.3%) and the mean maximum spinal cord dose was 40.7 GyE (range: 22.9-48 GyE). Based on dummy three-dimensional conformal radiotherapy planning, 12 patients were regarded as not being suitable for radical thoracic three-dimensional conformal radiotherapy. All the dose parameters of proton beam therapy, except for the esophageal dose, were lower than those for the dummy three-dimensional conformal radiotherapy plans. In comparison to the intensity-modulated radiotherapy plan, proton beam therapy also achieved dose reduction in the normal lung. None of the patients experienced grade 4 or worse non-hematological toxicities. Proton beam therapy for patients with stage III non-small cell lung cancer was feasible and was superior to three-dimensional conformal radiotherapy for several dosimetric parameters. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Amphetamine increases errors during episodic memory retrieval.

PubMed

Ballard, Michael Edward; Gallo, David A; de Wit, Harriet

2014-02-01

Moderate doses of stimulant drugs are known to enhance memory encoding and consolidation, but their effects on memory retrieval have not been explored in depth. In laboratory animals, stimulants seem to improve retrieval of emotional memories, but comparable studies have not been carried out in humans. In the present study, we examined the effects of dextroamphetamine (AMP) on retrieval of emotional and unemotional stimuli in healthy young adults, using doses that enhanced memory formation when administered before encoding in our previous study. During 3 sessions, healthy volunteers (n = 31) received 2 doses of AMP (10 and 20 mg) and placebo in counterbalanced order under double-blind conditions. During each session, they first viewed emotional and unemotional pictures and words in a drug-free state, and then 2 days later their memory was tested, 1 hour after AMP or placebo administration. Dextroamphetamine did not affect the number of emotional or unemotional stimuli remembered, but both doses increased recall intrusions and false recognition. Dextroamphetamine (20 mg) also increased the number of positively rated picture descriptions and words generated during free recall. These data provide the first evidence that therapeutic range doses of stimulant drugs can increase memory retrieval errors. The ability of AMP to positively bias recollection of prior events could contribute to its potential for abuse.

Amphetamine Increases Errors During Episodic Memory Retrieval

PubMed Central

Ballard, Michael Edward; Gallo, David A.; de Wit, Harriet

2014-01-01

Moderate doses of stimulant drugs are known to enhance memory encoding and consolidation, but their effects on memory retrieval have not been explored in depth. In laboratory animals, stimulants seem to improve retrieval of emotional memories, but comparable studies have not been carried out in humans. In the present study, we examined the effects of dextroamphetamine (AMP) on retrieval of emotional and unemotional stimuli in healthy young adults, using doses that enhanced memory formation when administered before encoding in our previous study. During 3 sessions, healthy volunteers (n = 31) received 2 doses of AMP (10 and 20 mg) and placebo in counter-balanced order under double-blind conditions. During each session, they first viewed emotional and unemotional pictures and words in a drug-free state, and then 2 days later their memory was tested, 1 hour after AMP or placebo administration. Dextroamphetamine did not affect the number of emotional or unemotional stimuli remembered, but both doses increased recall intrusions and false recognition. Dextroamphetamine (20 mg) also increased the number of positively rated picture descriptions and words generated during free recall. These data provide the first evidence that therapeutic range doses of stimulant drugs can increase memory retrieval errors. The ability of AMP to positively bias recollection of prior events could contribute to its potential for abuse. PMID:24135845

Characterization of a gated fiber-optic-coupled detector for application in clinical electron beam dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanyi, James A.; Nitzling, Kevin D.; Lodwick, Camille J.

2011-02-15

Purpose: Assessment of the fundamental dosimetric characteristics of a novel gated fiber-optic-coupled dosimetry system for clinical electron beam irradiation. Methods: The response of fiber-optic-coupled dosimetry system to clinical electron beam, with nominal energy range of 6-20 MeV, was evaluated for reproducibility, linearity, and output dependence on dose rate, dose per pulse, energy, and field size. The validity of the detector system's response was assessed in correspondence with a reference ionization chamber. Results: The fiber-optic-coupled dosimetry system showed little dependence to dose rate variations (coefficient of variation {+-}0.37%) and dose per pulse changes (with 0.54% of reference chamber measurements). The reproducibilitymore » of the system was {+-}0.55% for dose fractions of {approx}100 cGy. Energy dependence was within {+-}1.67% relative to the reference ionization chamber for the 6-20 MeV nominal electron beam energy range. The system exhibited excellent linear response (R{sup 2}=1.000) compared to reference ionization chamber in the dose range of 1-1000 cGy. The output factors were within {+-}0.54% of the corresponding reference ionization chamber measurements. Conclusions: The dosimetric properties of the gated fiber-optic-coupled dosimetry system compare favorably to the corresponding reference ionization chamber measurements and show considerable potential for applications in clinical electron beam radiotherapy.« less

A Dosimetric Model of Duodenal Toxicity After Stereotactic Body Radiotherapy for Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, James D.; Christman-Skieller, Claudia; Kim, Jeff

2010-12-01

Introduction: Dose escalation for pancreas cancer is limited by the tolerance of adjacent normal tissues, especially with stereotactic body radiotherapy (SBRT). The duodenum is generally considered to be the organ at greatest risk. This study reports on the dosimetric determinants of duodenal toxicity with single-fraction SBRT. Methods and Materials: Seventy-three patients with locally advanced unresectable pancreatic adenocarcinoma received 25 Gy in a single fraction. Dose-volume histogram (DVH) endpoints evaluated include V{sub 5} (volume of duodenum that received 5 Gy), V{sub 10}, V{sub 15}, V{sub 20}, V{sub 25}, and D{sub max} (maximum dose to 1 cm{sup 3}). Normal tissue complication probabilitymore » (NTCP) was evaluated with a Lyman model. Univariate and multivariate analyses were conducted with Kaplan-Meier and Cox regression models. Results: The median time to Grade 2-4 duodenal toxicity was 6.3 months (range, 1.6-11.8 months). The 6- and 12-month actuarial rates of toxicity were 11% and 29%, respectively. V{sub 10}-V{sub 25} and D{sub max} all correlated significantly with duodenal toxicity (p < 0.05). In particular, V{sub 15} {>=} 9.1 cm{sup 3} and V{sub 15} < 9.1 cm{sup 3} yielded duodenal toxicity rates of 52% and 11%, respectively (p = 0.002); V{sub 20} {>=} 3.3 cm{sup 3} and V{sub 20} < 3.3 cm{sup 3} gave toxicity rates of 52% and 11%, respectively (p = 0.002); and D{sub max} {>=} 23 Gy and D{sub max} < 23 Gy gave toxicity rates of 49% and 12%, respectively (p = 0.004). Lyman NTCP model optimization generated the coefficients m = 0.23, n = 0.12, and TD{sub 50} = 24.6 Gy. Only the Lyman NTCP model remained significant in multivariate analysis (p = 0.001). Conclusions: Multiple DVH endpoints and a Lyman NTCP model are strongly predictive of duodenal toxicity after SBRT for pancreatic cancer. These dose constraints will be valuable in future abdominal SBRT studies.« less

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study.

PubMed

Tsubokura, Masaharu; Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)-4.29 mSv), 0.37 mSv (range: ND-3.61 mSv), 0.22 mSv (range: ND-1.44 mSv), 0.20 mSv (range: ND-1.87 mSv), and 0.17 mSv (range: ND-0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04-0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses.

Proposed linear energy transfer areal detector for protons using radiochromic film

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, Rulon; Lin, Liyong; Fager, Marcus

2015-04-15

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured atmore » a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%–10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%–15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.« less

Feasibility and Initial Dosimetric Findings for a Randomized Trial Using Dose-Painted Multiparametric Magnetic Resonance Imaging–Defined Targets in Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bossart, Elizabeth L., E-mail: EBossart@med.miami.edu; Stoyanova, Radka; Sandler, Kiri

2016-06-01

Purpose: To compare dosimetric characteristics with multiparametric magnetic resonance imaging–identified imaging tumor volume (gross tumor volume, GTV), prostate clinical target volume and planning target volume, and organs at risk (OARs) for 2 treatment techniques representing 2 arms of an institutional phase 3 randomized trial of hypofractionated external beam image guided highly targeted radiation therapy. Methods and Materials: Group 1 (n=20) patients were treated before the trial inception with the standard dose prescription. Each patient had an additional treatment plan generated per the experimental arm. A total of 40 treatment plans were compared (20 plans for each technique). Group 2 (n=15)more » consists of patients currently accrued to the hypofractionated external beam image guided highly targeted radiation therapy trial. Plans were created as per the treatment arm, with additional plans for 5 of the group 2 experimental arm with a 3-mm expansion in the imaging GTV. Results: For all plans in both patient groups, planning target volume coverage ranged from 95% to 100%; GTV coverage of 89.3 Gy for the experimental treatment plans ranged from 95.2% to 99.8%. For both groups 1 and 2, the percent volumes of rectum/anus and bladder receiving 40 Gy, 65 Gy, and 80 Gy were smaller in the experimental plans than in the standard plans. The percent volume at 1 Gy per fraction and 1.625 Gy per fraction were compared between the standard and the experimental arms, and these were found to be equivalent. Conclusions: The dose per fraction to the OARs can be made equal even when giving a large simultaneous integrated boost to the GTV. The data suggest that a GTV margin may be added without significant dose effects on the OARs.« less

Estimation of patient radiation dose from whole body 18F- FDG PET/CT examination in cancer imaging: a preliminary study

NASA Astrophysics Data System (ADS)

Mahmud, M. H.; Nordin, A. J.; Saad, F. F. Ahmad; Fattah Azman, A. Z.

2014-11-01

This study aims to estimate the radiation effective dose resulting from whole body fluorine-18 flourodeoxyglucose Positron Emission Tomography (18F-FDG PET) scanning as compared to conservative Computed Tomography (CT) techniques in evaluating oncology patients. We reviewed 19 oncology patients who underwent 18F-FDG PET/CT at our centre for cancer staging. Internal and external doses were estimated using radioactivity of injected FDG and volume CT Dose Index (CTDIvol), respectively with employment of the published and modified dose coefficients. The median differences of dose among the conservative CT and PET protocols were determined using Kruskal Wallis test with p < 0.05 considered as significant. The median (interquartile range, IQR) effective doses of non-contrasted CT, contrasted CT and PET scanning protocols were 7.50 (9.35) mSv, 9.76 (3.67) mSv and 6.30 (1.20) mSv, respectively, resulting in the total dose of 21.46 (8.58) mSv. Statistically significant difference was observed in the median effective dose between the three protocols (p < 0.01). The effective doses of whole body 18F-FDG PET technique may be effective the lowest amongst the conventional CT imaging techniques.

MO-FG-204-04: How Iterative Reconstruction Algorithms Affect the NPS of CT Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, G; Liu, X; Dodge, C

2015-06-15

Purpose: To evaluate how the third generation model based iterative reconstruction (MBIR) compares with filtered back-projection (FBP), adaptive statistical iterative reconstruction (ASiR), and the second generation MBIR based on noise power spectrum (NPS) analysis over a wide range of clinically applicable dose levels. Methods: The Catphan 600 CTP515 module, surrounded by an oval, fat-equivalent ring to mimic patient size/shape, was scanned on a GE HD750 CT scanner at 1, 2, 3, 6, 12 and 19mGy CTDIvol levels with typical patient scan parameters: 120kVp, 0.8s, 40mm beam width, large SFOV, 0.984 pitch and reconstructed thickness 2.5mm (VEO3.0: Abd/Pelvis with Texture andmore » NR05). At each CTDIvol level, 10 repeated scans were acquired for achieving sufficient data sampling. The images were reconstructed using Standard kernel with FBP; 20%, 40% and 70% ASiR; and two versions of MBIR (VEO2.0 and 3.0). For evaluating the effect of the ROI spatial location to the Result of NPS, 4 ROI groups were categorized based on their distances from the center of the phantom. Results: VEO3.0 performed inferiorly comparing to VEO2.0 over all dose levels. On the other hand, at low dose levels (less than 3 mGy), it clearly outperformed ASiR and FBP, in NPS values. Therefore, the lower the dose level, the relative performance of MBIR improves. However, the shapes of the NPS show substantial differences in horizontal and vertical sampling dimensions. These differences may determine the characteristics of the noise/texture features in images, and hence, play an important role in image interpretation. Conclusion: The third generation MBIR did not improve over the second generation MBIR in term of NPS analysis. The overall performance of both versions of MBIR improved as compared to other reconstruction algorithms when dose was reduced. The shapes of the NPS curves provided additional value for future characterization of the image noise/texture features.« less

Impact of Peptide Transporter 1 on the Intestinal Absorption and Pharmacokinetics of Valacyclovir after Oral Dose Escalation in Wild-Type and PepT1 Knockout Mice

PubMed Central

Yang, Bei; Hu, Yongjun

2013-01-01

The primary objective of this study was to determine the in vivo absorption properties of valacyclovir, including the potential for saturable proton-coupled oligopeptide transporter 1 (PepT1)-mediated intestinal uptake, after escalating oral doses of prodrug within the clinical dose range. A secondary aim was to characterize the role of PepT1 on the tissue distribution of its active metabolite, acyclovir. [3H]Valacyclovir was administered to wild-type (WT) and PepT1 knockout (KO) mice by oral gavage at doses of 10, 25, 50, and 100 nmol/g. Serial blood samples were collected over 180 minutes, and tissue distribution studies were performed 20 minutes after a 25-nmol/g oral dose of valacyclovir. We found that the Cmax and area under the curve (AUC)0–180 of acyclovir were 4- to 6-fold and 2- to 3-fold lower, respectively, in KO mice for all four oral doses of valacyclovir. The time to peak concentration of acyclovir was 3- to 10-fold longer in KO compared with WT mice. There was dose proportionality in the Cmax and AUC0–180 of acyclovir in WT and KO mice over the valacyclovir oral dose range of 10–100 nmol/g (i.e., linear absorption kinetics). No differences were observed in the peripheral tissue distribution of acyclovir once these tissues were adjusted for differences in perfusing drug concentrations in the systemic circulation. In contrast, some differences were observed between genotypes in the concentrations of acyclovir in the distal intestine. Collectively, the findings demonstrate a critical role of intestinal PepT1 in improving the rate and extent of oral absorption for valacyclovir. Moreover, this study provides definitive evidence for the rational development of a PepT1-targeted prodrug strategy. PMID:23924683

Proton Therapy for Reirradiation of Progressive or Recurrent Chordoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Mark W., E-mail: mmcdona2@iuhealth.org; Indiana University Health Proton Therapy Center, Bloomington, Indiana; Linton, Okechuckwu R.

2013-12-01

Purpose: To report the results in patients reirradiated with proton therapy for recurrent or progressive chordoma, with or without salvage surgery. Methods and Materials: A retrospective review of 16 consecutive patients treated from 2005 to 2012 was performed. All patients had received at least 1 prior course of radiation therapy to the same area, and all but 1 patient had at least 1 surgical resection for disease before receiving reirradiation. At the time of recurrence or progression, half of the patients underwent additional salvage surgery before receiving reirradiation. The median prior dose of radiation was 75.2 Gy (range, 40-79.2 Gy).more » Six patients had received prior proton therapy, and the remainder had received photon radiation. The median gross tumor volume at the time of reirradiation was 71 cm{sup 3} (range, 0-701 cm{sup 3}). Reirradiation occurred at a median interval of 37 months after prior radiation (range, 12-129 months), and the median dose of reirradiation was 75.6 Gy (relative biological effectiveness [RBE]) (range. 71.2-79.2 Gy [RBE]), given in standard daily fractionation (n=14) or hyperfractionation (n=2). Results: The median follow-up time was 23 months (range, 6-63 months); it was 26 months in patients alive at the last follow-up visit (range, 12-63 months). The 2-year estimate for local control was 85%, overall survival 80%, chordoma-specific survival 88%, and development of distant metastases 20%. Four patients have had local progression: 3 in-field and 1 marginal. Late toxicity included grade 3 bitemporal lobe radionecrosis in 1 patient that improved with hyperbaric oxygen, a grade 4 cerebrospinal fluid leak with meningitis in 1 patient, and a grade 4 ischemic brainstem stroke (out of radiation field) in 1 patient, with subsequent neurologic recovery. Conclusions: Full-dose proton reirradiation provided encouraging initial disease control and overall survival for patients with recurrent or progressive chordoma, although additional toxicities may develop with longer follow-up times.« less

Mechanical properties of carbon steel depending on the rate of the dose build-up of nitrogen and argon ions

NASA Astrophysics Data System (ADS)

Vorob'ev, V. L.; Bykov, P. V.; Bayankin, V. Ya.; Shushkov, A. A.; Vakhrushev, A. V.

2014-08-01

The effect of pulsed irradiation with argons and nitrogen ions on the mechanical properties, morphology, and structure of the surface layers of carbon steel St3 (0.2% C, 0.4% Mn, 0.15% Si, and Fe for balance) has been investigated depending on the rate of dose build-up at an average ion current density of 10, 20, and 40 μA/cm2. It has been established that the fatigue life and microhardness of surface layers increase in the entire studied range of dose build-up rates. This seems to be due to the hardening of the surface layers, which resulted from the generation of radiation defects and the irradiation-dynamic effect of fast ions. The sample irradiated by argon ions at the lowest of the selected dose build-up rates j av = 10 μA/cm2 withstands the largest number of cycles to failure.

Comparison of the Efficacy and Safety of 2 Acetaminophen Dosing Regimens in Febrile Infants and Children: A Report on 3 Legacy Studies.

PubMed

Temple, Anthony R; Zimmerman, Brenda; Gelotte, Cathy; Kuffner, Edwin K

2017-01-01

Compare efficacy and safety of 10 to 15 mg/kg with 20 to 30 mg/kg acetaminophen in febrile children 6 months to ≤ 11 years from 3 double-blind, randomized, single or multiple dose studies. Doses were compared on sum of the temperature differences (SUMDIFF), maximum temperature difference (MAXDIFF), temperature differences at each time point, and dose by time interactions. Alanine aminotransferase (ALT) was evaluated in the 72-hour duration study. A single dose of acetaminophen 20 to 30 mg/kg produced a greater effect on temperature decrement and duration of antipyretic effect over 8 hours than a single dose of 10 to 15 mg/kg. When equivalent total doses (i.e., 2 doses of 10 to 15 mg/kg given at 4-hour intervals and 1 dose of 20 to 30 mg/kg) were given over the initial 8-hour period, there were no significant temperature differences. Over a 72-hour period, 10 to 15 mg/kg acetaminophen administered every 4 hours maintained a more consistent temperature decrement than 20 to 30 mg/kg acetaminophen administered every 8 hours. Following doses of 60 to 90 mg/kg/day for up to 72 hours, no child had a clinically important increase in ALT from baseline. The number of children with reported adverse events was similar between doses. Data demonstrate the antipyretic effect of acetaminophen is dependent on total dose over a given time interval. These 3 studies provide clinical evidence that the recommended standard acetaminophen dose of 10 to 15 mg/kg is a safe and effective dose for treating fever in pediatric patients when administered as a single dose or as multiple doses for up to 72 hours.

Reirradiation of Large-Volume Recurrent Glioma With Pulsed Reduced-Dose-Rate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adkison, Jarrod B.; Tome, Wolfgang; Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI

2011-03-01

Purpose: Pulsed reduced-dose-rate radiotherapy (PRDR) is a reirradiation technique that reduces the effective dose rate and increases the treatment time, allowing sublethal damage repair during irradiation. Patients and Methods: A total of 103 patients with recurrent glioma underwent reirradiation using PRDR (86 considered to have Grade 4 at PRDR). PRDR was delivered using a series of 0.2-Gy pulses at 3-min intervals, creating an apparent dose rate of 0.0667 Gy/min to a median dose of 50 Gy (range, 20-60) delivered in 1.8-2.0-Gy fractions. The mean treatment volume was 403.5 {+-} 189.4 cm{sup 3} according to T{sub 2}-weighted magnetic resonance imaging andmore » a 2-cm margin. Results: For the initial or upgraded Grade 4 cohort (n = 86), the median interval from the first irradiation to PRDR was 14 months. Patients undergoing PRDR within 14 months of the first irradiation (n = 43) had a median survival of 21 weeks. Those treated {>=}14 months after radiotherapy had a median survival of 28 weeks (n = 43; p = 0.004 and HR = 1.82 with a 95% CI ranging from 1.25 to 3.10). These data compared favorably to historical data sets, because only 16% of the patients were treated at first relapse (with 46% treated at the second relapse, 32% at the third or fourth relapse, and 4% at the fourth or fifth relapse). The median survival since diagnosis and retreatment was 6.3 years and 11.4 months for low-grade, 4.1 years and 5.6 months for Grade 3, and 1.6 years and 5.1 months for Grade 4 tumors, respectively, according to the initial histologic findings. Multivariate analysis revealed age at the initial diagnosis, initial low-grade disease, and Karnofsky performance score of {>=}80 to be significant predictors of survival after initiation of PRDR. Conclusion: PRDR allowed for safe retreatment of larger volumes to high doses with palliative benefit.« less

Treatment of renal failure in idiopathic membranous nephropathy with azathioprine and prednisolone.

PubMed

Brown, J H; Douglas, A F; Murphy, B G; Hill, C M; McNamee, P T; Nelson, W E; Doherty, C C

1998-02-01

Progressive deterioration in renal function occurs in 20-50% of patients with idiopathic membranous nephropathy (IMN). Several treatment regimens have been used to reverse this with varying effect and toxicity. Thirteen patients (10 males, 3 females, median age 56 years) with IMN and progressive renal failure were treated with oral prednisolone 20-60 mg/day and azathioprine 1.3-2.7 mg/kgBW/day. All patients were followed up for a minimum of 2 years with a median follow-up of 73 months (range 24-103 months). Ten patients responded to treatment with a fall in serum creatinine and renal function stabilized in the remainder. Two patients relapsed, one of whom responded to an increase in immunosuppression, the other is now on dialysis. Proteinuria has significantly reduced in 10 patients, and only four patients still have nephrotic-range proteinuria. Mean (+/- SE) peak pretreatment serum creatinine of 229 (+/- 161) mumol/l and urinary protein of 11.8 (+/- 1.8) g/24 have fallen to 163 (+/- 65) mumol/l and 3.25 (+/- 1.0) g/24 h after 12 months treatment (P < 0.005, Wilcoxon matched pairs test). Immunosuppressive treatment has been successfully withdrawn in four patients after intervals ranging from 12 to 60 months. Adverse effects, which occurred in 10 patients, have been mild and have not led to treatment withdrawal though dose reductions have been necessary in some patients. Oral prednisolone and low-dose azathioprine is an effective therapy for progressing renal failure due to IMN, and induces remission of nephrotic syndrome. Side-effects are less than other immunosuppressive regimens.

Correlation of dosimetric parameters obtained with the analytical anisotropic algorithm and toxicity of chest chemoradiation in lung carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cartier, Lysian; Auberdiac, Pierre; Khodri, Mustapha

The purpose of this study was to analyze and revisit toxicity related to chest chemoradiotherapy and to correlate these side effects with dosimetric parameters obtained using analytical anisotropic algorithm (AAA) in locally unresectable advanced lung cancer. We retrospectively analyzed data from 47 lung cancer patients between 2005 and 2008. All received conformal 3D radiotherapy using high-energy linear accelerator plus concomitant chemotherapy. All treatment planning data were transferred into Eclipse 8.05 (Varian Medical Systems, Palo Alto, CA) and dosimetric calculations were performed using AAA. Thirty-three patients (70.2%) developed acute pneumopathy after radiotherapy (grades 1 and 2). One patient (2.1%) presented withmore » grade 3 pneumopathy. Thirty-one (66%) presented with grades 1-2 lung fibrosis, and 1 patient presented with grade 3 lung fibrosis. Thirty-four patients (72.3%) developed grade 1-2 acute oesophagic toxicity. Four patients (8.5%) presented with grades 3 and 4 dysphagia, necessitating prolonged parenteral nutrition. Median prescribed dose was 64 Gy (range 50-74) with conventional fractionation (2 Gy per fraction). Dose-volume constraints were respected with a median V20 of 23.5% (maximum 34%) and a median V30 of 17% (maximum 25%). The median dose delivered to healthy contralateral lung was 13.1 Gy (maximum 18.1 Gy). At univariate analysis, larger planning target volume and V20 were significantly associated with the probability of grade {>=}2 radiation-induced pneumopathy (p = 0.022 and p = 0.017, respectively). No relation between oesophagic toxicity and clinical/dosimetric parameters could be established. Using AAA, the present results confirm the predictive value of the V20 for lung toxicity as already demonstrated with the conventional pencil beam convolution approach.« less

Fractionated irradiation of carbon beam and the isoeffect dose on acute reaction of skin

PubMed Central

Uzawa, Akiko; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Koda, Kana; Koike, Sachiko; Ando, Koichi; Furusawa, Yoshiya

2014-01-01

Purpose: The aim of this study was to clear any specific LETs cause change in skin reaction. We irradiated mice feet with mono-energetic and SOBP carbon ions, to obtain dose–response of early skin reaction at different LETs. Materials and methods: Mice: C3H/HeMsNrsf female mice aged 4 months old were used for this study. The animals were produced and maintained in specific pathogen-free (SPF) facilities. Irradiation: The mice right hind legs received daily fractionated irradiation ranged from single to six fractions. Carbon ions (12C6+) were accelerated by the HIMAC synchrotron to 290 MeV/u. Irradiation was conducted using horizontal carbon-ion beams with a dose rate of ∼3 Gy/min. We chose the LETs at entrance of plateau (20keV/μm) and the SOBP (proximal: 40 keV/μm, middle: 45 keV/μm, distal: 60 keV/μm, distal-end: 80 keV/μm). The reference beam was 137Cs gamma rays with a dose rate of 1.2 Gy/min. Skin reaction: Skin reaction of the irradiated legs was scored every other day, between the14th and 35th post-irradiation days. Our scoring scale consisted of seven steps, ranging from 0.5 to 3.5 [ 1]. The skin score analyzed a result by the method that described by Ando et al. [ 2]. The Fe-plot proposed by Douglas and Fowler was used as a multifraction linear quadratic model. A plot between the reciprocal of the isoeffect dose and the dose per fraction resulted in a straight line. Results: Required isoeffect total dose increased linearly with the fraction numbers on a semi-logarithmic chart at LET 20–60 keV/µm SOBP beam. The isoeffect total dose decreased with the increase in the LET. However, no increases in isoeffect total dose were observed at few fractionations at 80 keV/µm. (data not shown) Using an Fe-plot, we analyzed the isoeffect total dose to evaluate the dependence on Carbon beam, or gamma ray. When I irradiate it by gamma ray, an Fe-plot shows linearly. But, irradiated by Carbon beam, an Fe-plot bent at low fractions (Fig. 1). Conclusion: The LQ-model-based Fe-plot could not fit skin reaction at few fractions at high-LET. Clinical Trial Registration number if required: No.Fig. 1.The reciprocal of the isoeffect dose is plotted against the dose per fraction. (i) Gamma ray: Fe-plot was linear. (ii) C-ions: Fe-plot bent at low fractions.

Survival times for cats with hyperthyroidism treated with a 3.35 mCi iodine-131 dose: a retrospective study of 96 cases.

PubMed

Vagney, Marie; Desquilbet, Loic; Reyes-Gomez, Edouard; Delisle, Françoise; Devauchelle, Patrick; Rodriguez-Piñeiro, Maria Isabel; Rosenberg, Dan; de Fornel-Thibaud, Pauline

2018-06-01

Objectives Radioiodine ( 131 I) dose determination using radiotracer kinetic studies or scoring systems, and fixed relatively high 131 I dose (ie, 4 or 5 mCi) administration, are effective and associated with prolonged survival times for hyperthyroid cats. The latter method is less complicated but could expose patients and veterinary personnel to unnecessary levels of radiation. The aim of this study was to retrospectively evaluate the efficacy of a fixed 3.35 mCi 131 I dose for the treatment of 96 hyperthyroid cats with no length estimation for any palpated goitre ⩾20 mm, assess outcome and identify factors associated with survival. Methods Serum total thyroxine concentrations at diagnosis and at follow-up times, survival times and cause of death were recorded. Multivariable Cox regression analysis was used to identify factors associated with time to any cause of death from 131 I therapy initiation. Results Administration of a median (interquartile range) dose of 3.35 mCi (3.27-3.44 mCi) radioiodine was an effective treatment in 94/96 cats, but two cats remained hyperthyroid. No death related to hyperthyroidism was recorded. Median survival time was 3.0 years; the 1 and 2 year survival rates after 131 I therapy were 90% and 78%, respectively. Low body weight (⩽3.1 kg; adjusted hazard ratio [aHR] 5.88; 95% confidence interval [CI] 2.22-16.67; P <0.01) and male gender (aHR 2.63; 95% CI 1.01-7.14; P = 0.04) were independently associated with death, whereas age, prior treatment with antithyroid drugs, reason for treatment and pretreatment azotaemia were not. Conclusions and relevance This study suggests that a fixed 3.35 mCi 131 I dose treatment is effective for hyperthyroid cats with goitre(s) with a maximal length estimation <20 mm, that long-term survival can be achieved and that low body weight and male gender are significantly associated with shorter survival times.

Limited infant exposure to benznidazole through breast milk during maternal treatment for Chagas disease.

PubMed

García-Bournissen, Facundo; Moroni, Samanta; Marson, Maria Elena; Moscatelli, Guillermo; Mastrantonio, Guido; Bisio, Margarita; Cornou, Laura; Ballering, Griselda; Altcheh, Jaime

2015-01-01

Benznidazole (BNZ) is safe and effective for the treatment of paediatric Chagas disease. Treatment of adults is also effective in many cases, but discouraged in breastfeeding women because no information on BNZ transfer into breast milk is available. We aimed to evaluate the degree of BNZ transfer into breast milk in lactating women with Chagas disease. Prospective cohort study of lactating women with Chagas disease treated with BNZ administered for 30 days. Patients and their breastfed infants were evaluated at admission, the 7th and 30th day of treatment (and monthly thereafter, for 6 months). BNZ was measured in plasma and milk by high performance liquid chromatography. The protocol was registered in ClinicalTrials.gov (#NCT01547533). 12 lactating women with chronic Chagas disease were enrolled (median age 28.5 years, range 20-34). Median BNZ dose was 5.65 mg/kg/day twice daily. Five mothers had adverse drug events (45%), but no adverse drug reactions or any untoward outcomes were observed in the breastfed infants. Median milk BNZ concentration was 3.8 mg/L (range 0.3-5.9) and 6.26 mg/L (range 0.3-12.6) in plasma. Median BNZ milk to plasma ratio was 0.52 (range 0.3-2.79). Median relative BNZ dose received by the infant (assuming a daily breast milk intake of 150 mL/kg/day) was 12.3% of the maternal dose per kg (range 5.5%-17%). The limited transference of BNZ into breast milk and the reassuring normal clinical evaluation of the breastfed babies suggest that maternal BNZ treatment for Chagas disease during breast feeding is unlikely to present a risk for the breastfed infant. ClinicalTrials.gov NCT01547533. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

SU-E-T-44: Angular Dependence of Surface Dose Enhancement Measured On Several Inhomogeneities Using Radiochromic EBT3 Films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jansen, A; Schoenfeld, A; Poppinga, D

Purpose: The quantification of the relative surface dose enhancement in dependence on the angle of incidence and the atomic number Z of the surface material. Methods: Experiments were performed with slabs made of aluminum, titanium, copper, silver, dental gold and lead. The metal slabs with equal sizes of 1.0×8.0×8.8mm{sup 3} were embedded in an Octavius 4D phantom (PTW Freiburg, Germany). Radiochromic EBT3 films were used to measure the surface dose for angles of incidence ranging from 0° to 90°. The setup with the metals slabs at the isocenter was irradiated with acceleration voltages of 6MV and 10MV. Water reference measurementsmore » were taken under equal conditions. Results: The surface dose enhancement is highest for angles of incidence below 30° and drops significantly for higher. The surface dose enhancement produced by lead and dental gold at 6MV showed a peak of 65%. At 90°, the surface dose enhancement dropped to 15% for both materials. The surface dose enhancements for silver, copper, titanium and aluminum were 45%, 32%, 22% and 12% at 0°, respectively. At an angle of incidence of 80°, the values dropped to 22%, 18%, 12% und 6%. The values for 10MV were very similar. Lead and dental gold showed peaks of 65% und 60%. Their values dropped to 18% at an angle of 90°. The surface dose enhancements for silver, copper, titanium and aluminum were 45%, 30%, 20% and 8% at 0°. At 80° the values dropped to 30%, 20%, 12% and 5%. A dependence of the magnitude of the surface dose enhancement on the atomic number of the surface material can be seen, which is in consistence with literature. Conclusion: The results show that the surface dose enhancements near implant materials with high Z-values should be taken into consideration in radio therapy, even when the angle of incidence is flat.« less

Low-Dose Radiotherapy in Indolent Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rossier, Christine; Schick, Ulrike; Miralbell, Raymond

Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 monthsmore » (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.« less

An exponential model equation for thiamin loss in irradiated ground pork as a function of dose and temperature of irradiation

NASA Astrophysics Data System (ADS)

Fox, J. B.; Thayer, D. W.; Phillips, J. G.

The effect of low dose γ-irradiation on the thiamin content of ground pork was studied in the range of 0-14 kGy at 2°C and at radiation doses from 0.5 to 7 kGy at temperatures -20, 10, 0, 10 and 20°C. The detailed study at 2°C showed that loss of thiamin was exponential down to 0kGy. An exponential expression was derived for the effect of radiation dose and temperature of irradiation on thiamin loss, and compared with a previously derived general linear expression. Both models were accurate depictions of the data, but the exponential expression showed a significant decrease in the rate of loss between 0 and -10°C. This is the range over which water in meat freezes, the decrease being due to the immobolization of reactive radiolytic products of water in ice crystals.

Performance characteristics of the EPR dosimetry system with table sugar in radiotherapy applications.

PubMed

Mikou, M; Ghosne, N; El Baydaoui, R; Zirari, Z; Kuntz, F

2015-05-01

Performance characteristics of the megavoltage photon dose measurements with EPR and table sugar were analyzed. An advantage of sugar as a dosimetric material is its tissue equivalency. The minimal detectable dose was found to be 1.5Gy for both the 6 and 18MV photons. The dose response curves are linear up to at least 20Gy. The energy dependence of the dose response in the megavoltage energy range is very weak and probably statistically insignificant. Reproducibility of measurements of various doses in this range performed with the peak-to-peak and double-integral methods is reported. The method can be used in real-time dosimetry in radiation therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optimization of initial propofol bolus dose for EEG Narcotrend Index-guided transition from sevoflurane induction to intravenous anesthesia in children.

PubMed

Dennhardt, Nils; Boethig, Dietmar; Beck, Christiane; Heiderich, Sebastian; Boehne, Martin; Leffler, Andreas; Schultz, Barbara; Sümpelmann, Robert

2017-04-01

Sevoflurane induction followed by intravenous anesthesia is a widely used technique to combine the benefits of an easier and less traumatic venipuncture after sevoflurane inhalation with a recovery with less agitation, nausea, and vomiting after total intravenous anesthesia (TIVA). Combination of two different anesthetics may lead to unwanted burst suppression in the electroencephalogram (EEG) during the transition phase. The objective of this prospective clinical observational study was to identify the optimal initial propofol bolus dose for a smooth transition from sevoflurane induction to TIVA using the EEG Narcotrend Index (NI). Fifty children aged 1-8 years scheduled for elective pediatric surgery were studied. After sevoflurane induction and establishing of an intravenous access, a propofol bolus dose range 0-5 mg·kg -1 was administered at the attending anesthetist's discretion to maintain a NI between 20 and 64, and sevoflurane was stopped. Anesthesia was continued as TIVA with a propofol infusion dose of 15 mg·kg -1 ·h -1 for the first 15 min, followed by stepwise reduction according to McFarlan's pediatric infusion regime, and remifentanil 0.25 μg·kg -1 ·min -1 . Endtidal concentration of sevoflurane, NI, and hemodynamic data were recorded during the whole study period using a standardized case report form. Propofol plasma concentrations were calculated using the paedfusor dataset and a TIVA simulation program. Median endtidal concentration of sevoflurane at the time of administration of the propofol bolus was 5.1 [IQR 4.7-5.9] Vol%. The median propofol bolus dose was 1.2 [IQR 0.9-2.5] mg·kg -1 and median NI thereafter was 33 [IQR 23-40]. Nine children presented with a NI 13-20 and three children with burst suppression in the EEG (NI 0-12); all of them received an initial propofol bolus dose >2 mg·kg -1 . Regression equation demonstrated that NI 20-64 was achieved with a 95% probability when using a propofol bolus dose of 1 mg·kg -1 after sevoflurane induction. Decrease in mean arterial blood pressure correlated significantly with propofol bolus dose (P = 0.038). After 25 min of TIVA, children younger than 2 years had a higher NI (median difference 14.0, 95%CI: 6.0-20.0, P = 0.001), higher deviations from the expected Narcotend Index (median difference 4.1, 95%CI: 3.9-4.2, P < 0.001) and lower calculated propofol plasma concentrations (median difference 0.2 μg·ml -1 , 95% CI: 0.1-0.3 μg·ml -1 , P < 0.001) than older children. After sevoflurane induction, a reduced propofol bolus dose of 1 mg·kg -1 followed by TIVA according to McFarlan's regime resulted in a NI within the recommended range in children aged 1-8 years. During the course of TIVA, children younger than 2 years displayed higher NI values and more pronounced interindividual variation. Processed EEG monitoring is recommended to find adequate individual age-dependent doses. © 2017 John Wiley & Sons Ltd.

Monte Carlo simulation of TrueBeam flattening-filter-free beams using varian phase-space files: comparison with experimental data.

PubMed

Belosi, Maria F; Rodriguez, Miguel; Fogliata, Antonella; Cozzi, Luca; Sempau, Josep; Clivio, Alessandro; Nicolini, Giorgia; Vanetti, Eugenio; Krauss, Harald; Khamphan, Catherine; Fenoglietto, Pascal; Puxeu, Josep; Fedele, David; Mancosu, Pietro; Brualla, Lorenzo

2014-05-01

Phase-space files for Monte Carlo simulation of the Varian TrueBeam beams have been made available by Varian. The aim of this study is to evaluate the accuracy of the distributed phase-space files for flattening filter free (FFF) beams, against experimental measurements from ten TrueBeam Linacs. The phase-space files have been used as input in PRIMO, a recently released Monte Carlo program based on the PENELOPE code. Simulations of 6 and 10 MV FFF were computed in a virtual water phantom for field sizes 3 × 3, 6 × 6, and 10 × 10 cm(2) using 1 × 1 × 1 mm(3) voxels and for 20 × 20 and 40 × 40 cm(2) with 2 × 2 × 2 mm(3) voxels. The particles contained in the initial phase-space files were transported downstream to a plane just above the phantom surface, where a subsequent phase-space file was tallied. Particles were transported downstream this second phase-space file to the water phantom. Experimental data consisted of depth doses and profiles at five different depths acquired at SSD = 100 cm (seven datasets) and SSD = 90 cm (three datasets). Simulations and experimental data were compared in terms of dose difference. Gamma analysis was also performed using 1%, 1 mm and 2%, 2 mm criteria of dose-difference and distance-to-agreement, respectively. Additionally, the parameters characterizing the dose profiles of unflattened beams were evaluated for both measurements and simulations. Analysis of depth dose curves showed that dose differences increased with increasing field size and depth; this effect might be partly motivated due to an underestimation of the primary beam energy used to compute the phase-space files. Average dose differences reached 1% for the largest field size. Lateral profiles presented dose differences well within 1% for fields up to 20 × 20 cm(2), while the discrepancy increased toward 2% in the 40 × 40 cm(2) cases. Gamma analysis resulted in an agreement of 100% when a 2%, 2 mm criterion was used, with the only exception of the 40 × 40 cm(2) field (∼95% agreement). With the more stringent criteria of 1%, 1 mm, the agreement reduced to almost 95% for field sizes up to 10 × 10 cm(2), worse for larger fields. Unflatness and slope FFF-specific parameters are in line with the possible energy underestimation of the simulated results relative to experimental data. The agreement between Monte Carlo simulations and experimental data proved that the evaluated Varian phase-space files for FFF beams from TrueBeam can be used as radiation sources for accurate Monte Carlo dose estimation, especially for field sizes up to 10 × 10 cm(2), that is the range of field sizes mostly used in combination to the FFF, high dose rate beams.

Biological availability of (238)U, (234)U and (226)Ra for wild berries and meadow grasses in natural ecosystems of Belarus.

PubMed

Sokolik, G A; Ovsiannikova, S V; Voinikava, K V; Ivanova, T G; Papenia, M V

2014-01-01

This work is devoted to investigation of behavior of (234)U, (238)U and (226)Ra by determining the soil to plant transfer under different natural conditions such as forest or swamped areas and meadow lands with different soil types. The paper summarizes the data on investigation of uranium and radium uptake by wild berries and natural meadow grasses in the typical conditions of Belarus. Parameters characterizing the biological availability of (234)U, (238)U and (226)Ra for bilberry (Vaccinium myrtillus), lingonberry (Vaccinium viti-idaea), blueberry (Vaccinium iliginosum) and cranberry (Vaccinium oxycoccus palustris) as well as for widely occurring mixed meadow vegetation, which belongs to the sedge-grass or grass-sedge associations and forbs, have been established. In the sites under investigation, the deposition levels of (238+239+240)Pu were less than 0.37 kBq m(-2) and (137)Cs deposition ranged between less than 0.37 and 37 kBq m(-2). It was found that activity concentrations of radionuclides in berries varied in the ranges of 0.037-0.11 for (234)U, 0.036-0.10 for (238)U and 0.11-0.43 Bq kg(-1) for (226)Ra, but in the mixed meadow grasses they were 0.32-4.4, 0.24-3.9 and 0.14-6.9 Bq kg(-1) accordingly. The (234)U/(238)U activity ratios were 1.02 ± 0.01 for wild berries, 1.20 ± 0.09 for underground meadow grasses and 1.02 ± 0.02 for proper soils. The concentration ratios (CRs, dry weight basis) of (234)U and (238)U for mixed meadow grasses were 0.036-0.42 and 0.041-0.46 respectively. The correspondent geometric means (GM) were 0.13 and 0.15 with geometric standard deviations (GSD) of 2.4. The CRs of (226)Ra for meadow grasses were 0.031-1.0 with GM 0.20 and GSD 2.6. The CRs of (234)U, (238)U and (226)Ra for wild berries ranged within 0.0018-0.008 (GM is 0.0034, GSD is 1.8), 0.0018-0.008 (GM is 0.0035, GSD is 1.8) and 0.005-0.033 (GM is 0.016, GSD is 2.1) accordingly. The highest CR values of uranium for mixed meadow grasses were found in the sites with high-moor peat and sandy soils. The lowest CRs for grasses were common to loamy and peat-gley soils. The CRs for the same berry species in the sites with sandy soils exceeded the appropriate CR values in the sites with loamy soils by factors of 3-4 for uranium and 4-6 for radium. The data obtained on radionuclide accumulation by plants were used to estimate the average annual effective doses to the population from radionuclide intake through the "soil - wild berries - man" and "soil - meadow vegetation - animal - cow milk-beef - man" trophic chains. The effective doses resulting from (234)U, (238)U and (226)Ra intake with the wild berries for adults were estimated as 0.02-0.09 μSv y(-1) (GM is 0.044, GSD is 1.6). It was established that only in the territory with (137)Cs deposition of ∼1.0-1.5 kBq m(-2) the doses resulting from (234)U, (238)U and (226)Ra intake with wild berries can be comparable with corresponding doses from (137)Cs. In the territories with higher levels of (137)Cs deposition the doses resulting from its intake with the wild berries are usually over the summarized doses of uranium and (226)Ra. The total doses for adults resulting from uranium and (226)Ra intake with cow milk and beef ranged between 0.2 and 7.2 μSv y(-1) (GM is 2.0; GSD is 2.9) and the doses from (226)Ra usually exceeded the appropriate doses of uranium with a factor of 3-37. In the sites with (137)Cs deposition less than 3.7 kBq m(-2), the doses from (234)U, (238)U and (226)Ra intake with cow milk and beef were assessing as 1.1-7.2 μSv y(-1) and they were usually higher than the doses from (137)Cs, which were assessing as 0.4-3.2 μSv y(-1) for its deposition 2 kBq m(-2). In the territory with (137)Cs deposition 10-20 kBq m(-2) and higher, the internal doses resulting from (137)Cs intake with cow milk and beef (10-50 μSv y(-1)) exceeded the proper doses from natural (234)U, (238)U and (226)Ra. Copyright © 2013 Elsevier Ltd. All rights reserved.

Use of alternating and pulsed direct current electrified fields for zebra mussel control

USGS Publications Warehouse

Luoma, James A.; Dean, Jan C.; Severson, Todd J.; Wise, Jeremy K.; Barbour, Matthew

2017-01-01

Alternatives to chemicals for controlling dreissenid mussels are desirable for environmental compatibility, but few alternatives exist. Previous studies have evaluated the use of electrified fields for stunning and/or killing planktonic life stages of dreissenid mussels, however, the available literature on the use of electrified fields to control adult dreissenid mussels is limited. We evaluated the effects of sinusoidal alternating current (AC) and 20% duty cycle square-wave pulsed direct current (PDC) exposure on the survival of adult zebra mussels at water temperatures of 10, 15, and 22 °C. Peak voltage gradients of ~ 17 and 30 Vp/cm in the AC and PDC exposures, respectively, were continuously applied for 24, 48, or 72 h. Peak power densities ranged from 77,999 to 107,199 µW/cm3 in the AC exposures and 245,320 to 313,945 µW/cm3 in the PDC exposures. The peak dose ranged from 6,739 to 27,298 Joules/cm3 and 21,306 to 80,941 Joules/cm3 in the AC and PDC exposures, respectively. The applied power ranged from 16.6 to 68.9 kWh in the AC exposures and from 22.2 to 86.4 kWh in the PDC exposures. Mortality ranged from 2.7 to 92.7% in the AC exposed groups and from 24.0 to 98.7% in PDC exposed groups. Mortality increased with corresponding increases in water temperature and exposure duration, and we observed more zebra mussel mortality in the PDC exposures. Exposures conducted with AC required less of a peak dose (Joules/cm3) but more applied power (kWh) to achieve the same level of adult zebra mussel mortality as corresponding PDC exposures. The results demonstrate that 20% duty cycle square-wave PDC requires less energy than sinusoidal AC to inducing the same level of adult zebra mussel mortality.

Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

NASA Astrophysics Data System (ADS)

Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

2015-02-01

In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5-20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10-2, 1.48×10-2, 4.14×10-2, and 6.03×10-2, 9.44×10-2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose.

Imatinib dose reduction in patients with chronic myeloid leukemia in sustained deep molecular response.

PubMed

Cervantes, Francisco; Correa, Juan-Gonzalo; Pérez, Isabel; García-Gutiérrez, Valentín; Redondo, Sara; Colomer, Dolors; Jiménez-Velasco, Antonio; Steegmann, Juan-Luis; Sánchez-Guijo, Fermín; Ferrer-Marín, Francisca; Pereira, Arturo; Osorio, Santiago

2017-01-01

To determine whether a lower imatinib dose could minimize toxicity while maintaining the molecular response (MR), imatinib dose was reduced to 300 mg daily in 43 patients with chronic myeloid leukemia (CML) in sustained deep molecular response to first-line imatinib 400 mg daily. At the time of dose reduction, median duration of the deep response was 4.1 (interquartile range (IQR) 2.2-5.9) years; molecular response was MR 4 , MR 4.5 , and MR 5 of the international scale in 6, 28, and 9 patients, respectively. Toxicity grade was 1, 2, and 3 in 28, 8, and 1 patients, respectively; 6 patients underwent dose reduction without having side effects. With a median of 1.6 (IQR 0.7-3.2) years on imatinib 300 mg daily, only one patient lost the deep molecular response to MR 3 . At the last follow-up, response was MR 3 , MR 4 , MR 4.5 , and MR 5 in 1, 3, 9, and 30 patients, respectively. Toxicity improvement was observed in 23 (62.2 %) of the 37 patients with side effects, decreasing to grade 0 in 20 of them. All but one anemic patients improved (p = 0.01), the median Hb increase in this subgroup of patients being 1 g/dL. In CML patients with sustained deep response to the standard imatinib dose, reducing to 300 mg daily significantly improves tolerability and preserves efficacy.

An 8-Week Randomized, Double-Blind Trial Comparing Efficacy, Safety, and Tolerability of 3 Vilazodone Dose-Initiation Strategies Following Switch From SSRIs and SNRIs in Major Depressive Disorder

PubMed Central

Rele, Shilpa; Millet, Robert; Kim, Sungman; Paik, Jong-Woo; Kim, Seonghwan; Masand, Prakash S.

2015-01-01

Introduction: Vilazodone, a selective and potent 5-HT1A partial agonist and 5-HT reuptake inhibitor, has been approved for treatment of major depressive disorder (MDD) in adults. The primary objective of the study was to compare the efficacy and tolerability of switching to 3 different doses of vilazodone from an equivalent dose range of generic selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in adult subjects with MDD. Method: This was an 8-week, randomized, double-blind, parallel-group, 3-arm trial to compare vilazodone 10 mg/d, 20 mg/d, and 40 mg/d as starting doses. Data were collected from December 2012 to December 2013. There was no washout phase, prior medications were stopped at the baseline visit, and vilazodone was started the next day in adults with MDD (DSM-IV criteria). The 10-mg/d and 20-mg/d dose was increased to 40 mg/d by week 3 and week 1, respectively, and the 40-mg/d initiation dose continued unchanged. The primary efficacy measure was change in Montgomery-Asberg Depression Rating Scale (MADRS) score between the 3 dose groups. The secondary efficacy measures were changes in Clinical Global Impressions–Severity (CGI-S), CGI-Improvement (CGI-I), and Hamilton Anxiety Rating Scale (HARS) scores. Safety measures were obtained by spontaneously reported adverse events, vital signs recording, and laboratory tests. Multivariate tests were used for statistical analysis. Results: Seventy subjects were randomized, and 60 subjects completed the study (n = 20 in each group). Overall, there was a significant reduction in MADRS score from baseline (26.08 ± 1.1) to week 8 (9.86 ± 1.2) in the entire sample (P < .001). Similarly, there was a significant improvement in CGI-S (P < .001), CGI-I (P < .001) and HDRS (P < .001) scores from baseline to the end of the trial. There were no significant differences between the 3 vilazodone dose-initiation groups in changes in MADRS scores (P = .95) or changes in CGI-S (P = .83), CGI-I (P = .51), or HARS scores (P = .61). Dry mouth (n = 55), nausea (n = 10), and diarrhea (n = 5) were the most common side effects, with diarrhea reported in 5 subjects in the 40-mg/d initiation group. No serious adverse events were reported. Conclusions: The present study indicates the potential benefit of switching to vilazodone in patients with MDD who are inadequate responders to SSRIs or SNRIs. There were no meaningful differences in efficacy or tolerability between the 3 different dose-initiation strategies with vilazodone; however, diarrhea appeared to be more frequently reported with the 40-mg/d dose. Given the modest sample size, larger studies are required to confirm our findings. Trial Registration: ClinicalTrials.gov identifiers: NCT02015546 and NCT01473381 PMID:26693034

PET-Based Human Dosimetry of the Dimeric αvβ3 Integrin Ligand 68Ga-DOTA-E-[c(RGDfK)]2, a Potential Tracer for Imaging Tumor Angiogenesis.

PubMed

López-Rodríguez, Victoria; Galindo-Sarco, Carlos; García-Pérez, Francisco O; Ferro-Flores, Guillermina; Arrieta, Oscar; Ávila-Rodríguez, Miguel A

2016-03-01

Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for αvβ3 integrin receptors overexpressed in tumor cells. The objective of this research was to determine the biodistribution and estimate the radiation dose from (68)Ga-DOTA-E-[c(RGDfK)]2 using whole-body PET scans in humans. Five healthy volunteers (2 women, 3 men; mean age ± SD, 37.2 ± 15.6 y; range, 28-65 y; mean weight, 79.2 ± 21.0 kg; range, 64-115 kg) were included. After intravenous injection of the tracer (198.3 ± 3.3 MBq), 3 successive whole-body (vertex to mid thigh) PET/CT scans at 3 time points (30, 60, and 120 min) were obtained on a 16-slice PET/CT scanner. The subjects did not void the bladder until the entire series of images was completed. Low-dose CT without contrast agent was used for anatomic localization and attenuation correction. OLINDA/EXM software was applied to calculate human radiation doses using the reference adult model. The highest uptake was in the urinary bladder, followed by the liver, kidneys, and spleen, in descending order. The critical organ was the urinary bladder wall. The mean effective doses (all subjects, men and women) were 34.1 ± 4.9, 31.0 ± 2.4, and 20.9 ± 5.2 μSv/MBq for the no-voiding, 2.5-h-voiding, and 1-h-voiding models, respectively. Of particular interest in this research was the visualization of the choroid plexus and ventricular system, which seems to be a characteristic of RGD-dimeric peptides. Measured absorbed doses and effective doses are comparable to other previously reported RGD-based radiopharmaceuticals labeled with (68)Ga and (18)F. Therefore, (68)Ga-DOTA-E-[c(RGDfK)]2 can safely be used for imaging integrin αVβ3 expression. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

SU-C-207A-04: Accuracy of Acoustic-Based Proton Range Verification in Water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, KC; Sehgal, CM; Avery, S

2016-06-15

Purpose: To determine the accuracy and dose required for acoustic-based proton range verification (protoacoustics) in water. Methods: Proton pulses with 17 µs FWHM and instantaneous currents of 480 nA (5.6 × 10{sup 7} protons/pulse, 8.9 cGy/pulse) were generated by a clinical, hospital-based cyclotron at the University of Pennsylvania. The protoacoustic signal generated in a water phantom by the 190 MeV proton pulses was measured with a hydrophone placed at multiple known positions surrounding the dose deposition. The background random noise was measured. The protoacoustic signal was simulated to compare to the experiments. Results: The maximum protoacoustic signal amplitude at 5more » cm distance was 5.2 mPa per 1 × 10{sup 7} protons (1.6 cGy at the Bragg peak). The background random noise of the measurement was 27 mPa. Comparison between simulation and experiment indicates that the hydrophone introduced a delay of 2.4 µs. For acoustic data collected with a signal-to-noise ratio (SNR) of 21, deconvolution of the protoacoustic signal with the proton pulse provided the most precise time-of-flight range measurement (standard deviation of 2.0 mm), but a systematic error (−4.5 mm) was observed. Conclusion: Based on water phantom measurements at a clinical hospital-based cyclotron, protoacoustics is a potential technique for measuring the proton Bragg peak range with 2.0 mm standard deviation. Simultaneous use of multiple detectors is expected to reduce the standard deviation, but calibration is required to remove systematic error. Based on the measured background noise and protoacoustic amplitude, a SNR of 5.3 is projected for a deposited dose of 2 Gy.« less

Weight changes and their associations with demographic and clinical characteristics in risperidone maintenance treatment for schizophrenia.

PubMed

Xiang, Y-T; Wang, C-Y; Ungvari, G S; Kreyenbuhl, J A; Chiu, H F K; Lai, K Y C; Lee, E H M; Bo, Q-J; Dixon, L B

2011-06-01

This study aimed to characterize weight changes in schizophrenia patients taking risperidone as part of a randomized, controlled, open-label clinical trial. A total of 374 patients with schizophrenia who had been clinically stabilized following an acute episode were randomly assigned to a 'no-dose-reduction' group (initial optimal therapeutic doses continued throughout the study), a '4-week group' (initial optimal therapeutic doses continued for 4 weeks followed by a half dose reduction that was maintained until the end of the study) or a '26-week group' (initial optimal therapeutic doses continued for 26 weeks followed by a half dose reduction until the end of the study). Participants were assessed monthly using standardized assessment instruments during the first 6 months, and then every 2 months until the last recruited patient completed the 1-year follow-up. Weight gain was defined as gaining at least 7% of initial body weight, weight loss as losing at least 7% of initial body weight. A BMI <18.5 kg m⁻² was defined as underweight, 18.5-24.9 kg m⁻² as normal range, and ≥ 25 kg m⁻² as overweight or obese. At the end of follow-up, of the patients who started within the underweight range (n=22), 77.3% gained weight, whereas 4.5% lost weight. The corresponding figures were 39.6% and 4.8% in patients who started at normal weight (n=273), respectively, and 17.7% and 17.7% in patients who started at overweight (n=79), respectively. At the same time, 59.1% of the patients who started at underweight range went into the normal weight and 13.6% into the overweight/obese range, respectively, while 24.5% of those who started at normal weight went into the overweight/obese range, and 1.1% into underweight range, respectively; 20.3% of those who started at overweight range went into normal weight at the end of the follow-up. Multiple logistic regression analyses revealed that being underweight or normal weight at study entry predicted weight gain compared to being overweight, whereas being overweight at entry was associated with a higher likelihood of weight loss compared to being normal weight. No correlation was found between weight change and dose reduction. Weight change is a common, long-term, but heterogeneous side effect in risperidone maintenance treatment for stable schizophrenia patients. Special attention should be paid to fluctuations in weight that may occur throughout the course of treatment with risperidone. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of Acute Gamma Irradiation on Curcuma alismatifolia Varieties and Detection of DNA Polymorphism through SSR Marker

PubMed Central

Taheri, Sima; Abdullah, Thohirah Lee; Ahmad, Zaiton; Abdullah, Nur Ashikin Psyquay

2014-01-01

The effects of eight different doses (0, 10, 20, 25, 35, 40, 60, and 100 Gy) of acute gamma irradiation on 44 (three varieties of Curcuma alismatifolia: Chiang Mai Red, Sweet Pink, Kimono Pink, and one Curcuma hybrid (Doi Tung 554) individual plants were investigated. Radiation sensitivity tests revealed that the LD50 values of the varieties were achieved at 21 Gy for Chiang Mai Red, 23 Gy for Sweet Pink, 25 Gy for Kimono Pink, and 28 Gy for Doi Tung 554. From the analysis of variance (ANOVA), significant variations were observed for vegetative traits, flowering development, and rhizome characteristics among the four varieties of Curcuma alismatifolia and dose levels as well as the dose × variety interaction. In irradiated plants, the leaf length, leaf width, inflorescence length, the number of true flowers, the number of pink bracts, number of shoots, plant height, rhizome size, number of storage roots, and number of new rhizomes decreased significantly (P < 0.05) as the radiation dose increased. The cophenetic correlation coefficient (CCC) between genetic dissimilarity matrix estimated from the morphological characters and the UPGMA clustering method was r = 0.93, showing a proof fit. In terms of genetic variation among the acutely irradiated samples, the number of presumed alleles revealed by simple sequence repeats ranged from two to seven alleles with a mean value of 3.1, 4.5, and 5.3 alleles per locus for radiation doses of 0, 10, and 20 Gy, respectively. The average values of the effective number of alleles, Nei's gene diversity, and Shannon's information index were 2.5–3.2, 0.51–0.66, and 0.9–1.3, respectively. The constructed dendrogram grouped the entities into seven clusters. Principal component analysis (PCA) supported the clustering results. Consequently, it was concluded that irradiation with optimum doses of gamma rays efficiently induces mutations in Curcuma alismatifolia varieties. PMID:24719878

Effect of acute gamma irradiation on Curcuma alismatifolia varieties and detection of DNA polymorphism through SSR marker.

PubMed

Taheri, Sima; Abdullah, Thohirah Lee; Ahmad, Zaiton; Abdullah, Nur Ashikin Psyquay

2014-01-01

The effects of eight different doses (0, 10, 20, 25, 35, 40, 60, and 100 Gy) of acute gamma irradiation on 44 (three varieties of Curcuma alismatifolia: Chiang Mai Red, Sweet Pink, Kimono Pink, and one Curcuma hybrid (Doi Tung 554) individual plants were investigated. Radiation sensitivity tests revealed that the LD50 values of the varieties were achieved at 21 Gy for Chiang Mai Red, 23 Gy for Sweet Pink, 25 Gy for Kimono Pink, and 28 Gy for Doi Tung 554. From the analysis of variance (ANOVA), significant variations were observed for vegetative traits, flowering development, and rhizome characteristics among the four varieties of Curcuma alismatifolia and dose levels as well as the dose × variety interaction. In irradiated plants, the leaf length, leaf width, inflorescence length, the number of true flowers, the number of pink bracts, number of shoots, plant height, rhizome size, number of storage roots, and number of new rhizomes decreased significantly (P < 0.05) as the radiation dose increased. The cophenetic correlation coefficient (CCC) between genetic dissimilarity matrix estimated from the morphological characters and the UPGMA clustering method was r = 0.93, showing a proof fit. In terms of genetic variation among the acutely irradiated samples, the number of presumed alleles revealed by simple sequence repeats ranged from two to seven alleles with a mean value of 3.1, 4.5, and 5.3 alleles per locus for radiation doses of 0, 10, and 20 Gy, respectively. The average values of the effective number of alleles, Nei's gene diversity, and Shannon's information index were 2.5-3.2, 0.51-0.66, and 0.9-1.3, respectively. The constructed dendrogram grouped the entities into seven clusters. Principal component analysis (PCA) supported the clustering results. Consequently, it was concluded that irradiation with optimum doses of gamma rays efficiently induces mutations in Curcuma alismatifolia varieties.

Bone Marrow Sparing in Intensity Modulated Proton Therapy for Cervical Cancer: Efficacy and Robustness under Range and Setup Uncertainties

PubMed Central

Dinges, Eric; Felderman, Nicole; McGuire, Sarah; Gross, Brandie; Bhatia, Sudershan; Mott, Sarah; Buatti, John; Wang, Dongxu

2015-01-01

Background and Purpose This study evaluates the potential efficacy and robustness of functional bone marrow sparing (BMS) using intensity-modulated proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic toxicity. Material and Methods IMPT plans with prescription dose of 45 Gy were generated for ten patients who have received BMS intensity-modulated x-ray therapy (IMRT). Functional bone marrow was identified by 18F-flourothymidine positron emission tomography. IMPT plans were designed to minimize the volume of functional bone marrow receiving 5–40 Gy while maintaining similar target coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with ±3% range uncertainty errors and/or ±3mm translational setup errors in all three principal dimensions. Results In the static scenario, the median dose volume reductions for functional bone marrow by IMPT were: 32% for V5GY, 47% for V10Gy, 54% for V20Gy, and 57% for V40Gy, all with p<0.01 compared to IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for V5Gy, 37% for V10Gy, 41% for V20Gy, and 39% for V40Gy, all with p<0.01. Conclusions The potential sparing of functional bone marrow by IMPT for cervical cancer is significant and robust under realistic systematic range uncertainties and clinically relevant setup errors. PMID:25981130

Analysis of dose-volume parameters predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-conformal radiation therapy or IMRT.

PubMed

Kumar, Gaurav; Rawat, Sheh; Puri, Abhishek; Sharma, Manoj Kumar; Chadha, Pranav; Babu, Anand Giri; Yadav, Girigesh

2012-01-01

Multimodality therapy for esophageal cancer can cause various kinds of treatment-related sequelae, especially pulmonary toxicities. This prospective study aims to investigate the clinical and dosimetric parameters predicting lung injury in patients undergoing radiation therapy for esophageal cancer. Forty-five esophageal cancer patients were prospectively analyzed. The pulmonary toxicities (or sequelae) were evaluated by comparing chest X-ray films, pulmonary function tests and symptoms caused by pulmonary damage before and after treatment. All patients were treated with either three-dimensional radiotherapy (3DCRT) or with intensity-modulated radiotherapy (IMRT). The planning dose volume histogram was used to compute the lung volumes receiving more than 5, 10, 20 and 30 Gy (V5, V10, V20, V30) and mean lung dose. V20 was larger in the IMRT group than in the 3DCRT group (p = 0.002). V20 (>15%) and V30 (>20%) resulted in a statistically significant increase in the occurrence of chronic pneumonitis (p = 0.03) and acute pneumonitis (p = 0.007), respectively. The study signifies that a larger volume of lung receives lower doses because of multiple beam arrangement and a smaller volume of lung receives higher doses because of better dose conformity in IMRT plans. Acute pneumonitis correlates more with V30 values, whereas chronic pneumonitis was predominantly seen in patients with higher V20 values.

SU-F-T-129: Impact of Radial Fluctuations in RBE for Therapeutic Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butkus, M; Palmer, T

Purpose: To evaluate the off axis relative biological effectiveness (RBE) for actively scanned proton beams and determine if a constant radial RBE can be assumed. Methods: The PHITS Monte Carlo code paired with a microscopic analytical function was used to determine probability distribution functions of the lineal energy in 0.3µm diameter spheres throughout a water phantom. Twenty million primary protons were simulated for a 0.6cm diameter pencil beam. Beam energies corresponding to Bragg Peak depths of 50, 100, 150, 200, 250, and 300mm were used and evaluated transversely every millimeter and radially for annuli of 1.0, 2.0, 3.0, 3.2, 3.4,more » 3.6, 4.0, 5.0, 10.0, 15.0, 20.0 and 25.0mm outer radius. The acquired probability distributions were reduced to dose-mean lineal energies and applied to the modified microdosimetric kinetic model, for human submandibular gland (HSG) cells, to calculate relative biological effectiveness (RBE) compared to 60Co beams at the 10% survival threshold. Results: RBE was generally seen to increase as distance from the central axis (CAX) increased. However, this increase was only seen in low dose regions and its overall effects on the transverse biological dose remains low. In the entrance region of the phantom (10mm depth), minimum and maximum calculated RBEs varied between 15.22 and 18.88% for different energies. At the Bragg peak, this difference ranged from 3.15 to 26.77%. Despite these rather large variations the dose-weighted RBE and the CAX RBE varied by less than 0.14% at 10mm depth and less than 0.16% at the Bragg peak. Similarly small variations were found at all depths proximal of the Bragg peak. Conclusion: Although proton RBE does vary radially, its overall effect on biological dose is minimal and the use of a radially constant RBE in treatment planning for scanned proton beams would not produce large errors.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, S; Zheng, Y; Albani, D

Purpose: To reduce internal target volume (ITV), respiratory management is a must in imaging and treatment for lung, liver, and breast cancers. We investigated the dosimetric accuracy of VMAT treatment delivery with a Response™ gating system linked to linear accelerator. Methods: The Response™ gating module designed to directly control radiation beam by breath-holding with a ABC system (Elekta AB, Stockholm, Sweden) was tested for VMAT treatments. Seven VMAT plans including three conventional and four stereotactic body radiotherapy (SBRT) cases were evaluated. Each plan was composed of two or four arcs of 6MV radiation beam with prescribed dose ranged from 1.8more » to 9 Gy per fraction. Each plan was delivered continuously without gating and delivered with multiple interruptions by the ResponseTM gating module with a 20 or 30 second breath-holding period. MapCheck2 and Gafchromic EBT3 films sandwiched in MapPHAN were used to measure the delivered dose with and without gating. Films were scanned on a flatbed color scanner, and red channel was extracted for film dosimetry. Gamma analysis was performed to analyze the dosimetrical accuracy of the radiation delivery with gating. Results: The measured doses with gating remarkably agree with the planned dose distributions in the results of gamma index passing rate (within 20% isodose; >98% for 3%/3mm and >92% for 2%/2mm in MapCheck2, and >91% for 3%/3mm criteria in EBT3 film except one case which was for large target and highly modulated). No significant difference (student t-test: p-value < 0.0005) was shown between the doses delivered with and without gating. There was no indication of radiation gap or overlapping during deliver interruption in film dosimetry. Conclusion: The Response™ gating system can be safely used during VMAT treatment. The accurate performance of the gating system linked to ABC can contribute to ITV reduction for SBRT using VMAT.« less

Considerations on the calibration of small thermoluminescent dosimeters used for measurement of beta particle absorbed doses in liquid environments.

PubMed

Demidecki, A J; Williams, L E; Wong, J Y; Wessels, B W; Yorke, E D; Strandh, M; Strand, S E

1993-01-01

An investigation has been carried out on the factors which affect the absolute calibration of thermoluminescent dosimeters (TLDs) used in beta particle absorbed dose evaluations. Four effects on light output (LO) were considered: decay of detector sensitivity with time, finite TLD volume, dose linearity, and energy dependence. Most important of these was the decay of LO with time in culture medium, muscle tissue, and gels. This permanent loss of sensitivity was as large as an order of magnitude over a 21-day interval for the nominally 20-microns-thick disc-shaped CaSO4(Dy) TLDs in gel. Associated leaching of the dosimeter crystals out of the Teflon matrix was observed using scanning electron microscopy. Large channels leading from the outside environment into the TLDs were identified using SEM images. A possibility of batch dependence of fading was indicated. The second most important effect was the apparent reduction of light output due to finite size and increased specific gravity of the dosimeter (volume effect). We estimated this term by calculations as 10% in standard "mini" rods for beta particles from 90Y, but nearly a factor of 3 for 131I beta particles in the same geometry. No significant nonlinearity of the log (light output) with log (absorbed dose) over the range 0.05-20.00 Gy was discovered. Energy dependence of the LO was found to be not detectable, within measurement errors, over the range of 0.60-6.0 MeV mean energy electrons. With careful understanding of these effects, calibration via gel phantom would appear to be an acceptable strategy for mini TLDs used in beta absorbed dose evaluations in media.(ABSTRACT TRUNCATED AT 250 WORDS)

SU-F-T-416: Dosimetric Comparison of Coplanar and Non-Coplanar IMRT Plans for Peripheral Lung Lesion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, J; Zhang, S; Philbrook, S

2016-06-15

Purpose: The purpose of this study was to compare dosimetric parameters of treatment plans between coplanar and non-coplanar techniques for treating peripheral lung lesions. Methods: The planning CT scans of 6 patients in supine positions were used in this study. The size of the PTV ranges from 163 c.c. to 782 c.c.. The locations of PTV are mostly at the peripheral of Lung, some spreading to the mediastinum. For each patient, we generated two IMRT plans, one with and the other without non-coplanar beams. The non-coplanar beams were carefully selected so that the beams would never exit patient bodies throughmore » the contralateral lung. The IMRT plans were generated with Pinnacle 9.8 treatment planning software. The IMRT optimization objectives were kept the same for the corresponding pairs of plans. All plans were normalized such that 95% of PTV receives the prescription dose (full dose). Results: The conformity index (mean±standard deviation of the mean) is 1.49±0.14 and 1.58±0.23 for the coplanar and noncoplanar plans, respectively. The heterogeneity index (mean±standard deviation of the mean) is 7.74 ±2.33 and 6.34±1.40 for the coplanar and non-coplanar plans, respectively. The maximum heart dose is 60.94±6.22 and 60.42±7.21 Gy, and mean heart dose is 10.22 ±7.57, 9.07 ±6.32 Gy, for the coplanar and non-coplanar plans, respectively. The ipsilateral lung V20 is 48.0%±2.4% and 47.5%±3.3%, and V5 is 68.2%±10.0% and 69.1%±7.3%, for the coplanar and noncoplanar plans, respectively. Furthermore, with the non-coplanar beam arrangement, the contralateral lung V20 was reduced from 3.3%±3.7% to 1.3%±0.8%, and the contralateral Lung V5 is reduced significantly from 65.6%±9.3% to 33.5%±20.9% (p value =0.008). Conclusion: The IMRT plans with non-coplanar beam arrangement could reduce the exit dose to the contralateral lung, and therefore reduce the contralateral lung V5 significantly. This method is especially helpful while the lung lesion doesn’t have a symmetric shape.« less

The Impact of AUC-Based Monitoring on Pharmacist-Directed Vancomycin Dose Adjustments in Complicated Methicillin-Resistant Staphylococcus aureus Infection.

PubMed

Stoessel, Andrew M; Hale, Cory M; Seabury, Robert W; Miller, Christopher D; Steele, Jeffrey M

2018-01-01

This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution. A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L. Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation ( P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107). The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

Characteristics of an OSLD in the diagnostic energy range.

PubMed

Al-Senan, Rani M; Hatab, Mustapha R

2011-07-01

Optically stimulated luminescence (OSL) dosimetry has been recently introduced in radiation therapy as a potential alternative to the thermoluminescent dosimeter (TLD) system. The aim of this study was to investigate the feasibility of using OSL point dosimeters in the energy range used in diagnostic imaging. NanoDot OSL dosimeters (OSLDs) were used in this study, which started with testing the homogeneity of a new packet of nanoDots. Reproducibility and the effect of optical treatment (bleaching) were then examined, followed by an investigation of the effect of accumulated dose on the OSLD indicated doses. OSLD linearity, angular dependence, and energy dependence were also studied. Furthermore, comparison with LiF:Mg,Ti TLD chips using standard CT dose phantoms at 80 and 120 kVp settings was performed. Batch homogeneity showed a coefficient of variation of <5%. Single-irradiation measurements with bleaching after each OSL readout was found to be associated with a 3.3% reproducibility (one standard deviation measured with a 8 mGy test dose), and no systematic change in OSLDs sensitivity could be noted from measurement to measurement. In contrast, the multiple-irradiation readout without bleaching in between measurements was found to be associated with an uncertainty (using a 6 mGy test dose) that systematically increased with accumulated dose, reaching 42% at 82 mGy. Good linearity was shown by nanoDots under general x-ray, CT, and mammography units with an R2 > 0.99. The angular dependence test showed a drop of approximately 70% in the OSLD response at 90 degrees in mammography (25 kVp). With the general radiography unit, the maximum drop was 40% at 80 kVp and 20% at 120 kVp, and it was only 10% with CT at both 80 and 120 kVp. The energy dependence study showed a range of ion chamber-to-OSLDs ratios between 0.81 and 1.56, at the energies investigated (29-62 keV). A paired t-test for comparing the OSLDs and TLDs showed no significant variation (p > 0.1). OSLDs exhibited good batch homogeneity (<5%) and reproducibility (3.3%), as well as a linear response. In addition, they showed no statistically significant difference with TLDs in CT measurements (p > 0.1). However, high uncertainty (42%) in the dose estimate was found as a result of relatively high accumulated dose. Furthermore, nanoDots showed high angular dependence (up to 70%) in low kVp techniques. Energy dependence of about 60% was found, and correction factors were suggested for the range of energies investigated. Therefore, if angular and energy dependences are taken into consideration and the uncertainty associated with accumulated dose is avoided, OSLDs (nanoDots) can be suitable for use as point dosimeters in diagnostic settings.

The characteristics of dose at mass interface on lung cancer Stereotactic Body Radiotherapy (SBRT) simulation

NASA Astrophysics Data System (ADS)

Wulansari, I. H.; Wibowo, W. E.; Pawiro, S. A.

2017-05-01

In lung cancer cases, there exists a difficulty for the Treatment Planning System (TPS) to predict the dose at or near the mass interface. This error prediction might influence the minimum or maximum dose received by lung cancer. In addition to target motion, the target dose prediction error also contributes in the combined error during the course of treatment. The objective of this work was to verify dose plan calculated by adaptive convolution algorithm in Pinnacle3 at the mass interface against a set of measurement. The measurement was performed using Gafchromic EBT 3 film in static and dynamic CIRS phantom with amplitudes of 5 mm, 10 mm, and 20 mm in superior-inferior motion direction. Static and dynamic phantom were scanned with fast CT and slow CT before planned. The results showed that adaptive convolution algorithm mostly predicted mass interface dose lower than the measured dose in a range of -0,63% to 8,37% for static phantom in fast CT scanning and -0,27% to 15,9% for static phantom in slow CT scanning. In dynamic phantom, this algorithm was predicted mass interface dose higher than measured dose up to -89% for fast CT and varied from -17% until 37% for slow CT. This interface of dose differences caused the dose mass decreased in fast CT, except for 10 mm motion amplitude, and increased in slow CT for the greater amplitude of motion.

Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial.

PubMed

Beaudoin, Francesca L; Lin, Charlie; Guan, Wentao; Merchant, Roland C

2014-11-01

Low-dose ketamine has been used perioperatively for pain control and may be a useful adjunct to intravenous (IV) opioids in the control of acute pain in the emergency department (ED). The aim of this study was to determine the effectiveness of low-dose ketamine as an adjunct to morphine versus standard care with morphine alone for the treatment of acute moderate to severe pain among ED patients. A double-blind, randomized, placebo-controlled trial with three study groups was conducted at a large, urban academic ED over a 10-month period. Eligible patients were 18 to 65 years old with acute moderate to severe pain (score of at least 5 out of 10 on the numerical pain rating scale [NRS] and pain duration < 7 days) who were deemed by their treating physician to require IV opioids. The three study groups were: 1) morphine and normal saline placebo (standard care group), 2) morphine and 0.15 mg/kg ketamine (group 1), or 3) morphine and 0.3 mg/kg ketamine (group 2). Participants were assessed at 30, 60, and 120 minutes after study medication administration and received rescue analgesia as needed to target a 50% reduction in pain. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the NRS and calculated as the summed pain-intensity (SPID) difference over 2 hours. The amount and timing of rescue opioid analgesia was evaluated as a secondary outcome. The occurrence of adverse events was also measured. Sixty patients were enrolled (n = 20 in each group). There were no differences between study groups with respect to age, sex, race/ethnicity, preenrollment analgesia, or baseline NRS. Over the 2-hour poststudy medication administration period, the SPIDs were higher (greater pain relief) for the ketamine study groups than the control group (standard care 4.0, interquartile range [IQR] = 1.8 to 6.5; group 1 7.0, IQR = 4.3 to 10.8; and group 2 7.8, IQR = 4.8 to 12.8; p < 0.02). The SPIDs for the ketamine groups were similar (p < 0.46). When compared to standard care, group 2 sustained the reduction in pain intensity up to 2 hours, whereas group 1 was similar to standard care by 2 hours. Similar numbers of patients received rescue analgesia: standard care group, seven of 20, 35%; group 1, four of 20, 20%; and group 2, four of 20, 20% (p = 0.48). Among those receiving rescue analgesia, those in the standard care group received analgesia sooner than either low-dose ketamine group, on average. More participants in the low-dose ketamine groups reported dysphoria and dizziness. Low-dose ketamine is a viable analgesic adjunct to morphine for the treatment of moderate to severe acute pain. Dosing of 0.3 mg/kg is possibly more effective than 0.15 mg/kg, but may be associated with minor adverse events. Future studies should evaluate additional outcomes, optimum dosing, and use in specific populations. © 2014 by the Society for Academic Emergency Medicine.

Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer.

PubMed

Marshall, John; Shapiro, Geoffrey I; Uttenreuther-Fischer, Martina; Ould-Kaci, Mahmoud; Stopfer, Peter; Gordon, Michael S

2013-02-01

To determine the maximum tolerated dose (MTD), safety and anti-tumor activity of afatinib combined with docetaxel in advanced cancer. The MTD was determined from dose-limiting toxicities in the first cycle. Thirty-one patients received 10, 20 and 30 mg oral afatinib, plus 60 and 75 mg/m(2) intravenous docetaxel (six cohorts; 3-week cycles). The MTD of afatinib was 20 mg/day (days 2-21) with 75 mg/m(2) docetaxel (day 1). Dose-limiting toxicities were grade 3/4 diarrhea (n = 3) and febrile neutropenia (n = 6). Most frequently occurring adverse events were diarrhea, neutropenia and rash. Disease stabilization occurred in 14 patients. Afatinib 20 mg/day plus docetaxel was suboptimal and the study could not yield Phase II dose recommendations. The combination resulted in a manageable safety profile.

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

The dichotomy of memantine treatment for ischemic stroke: dose-dependent protective and detrimental effects

PubMed Central

Trotman, Melissa; Vermehren, Philipp; Gibson, Claire L; Fern, Robert

2015-01-01

Excitotoxicity is a major contributor to cell death during the acute phase of ischemic stroke but aggressive pharmacological targeting of excitotoxicity has failed clinically. Here we investigated whether pretreatment with low doses of memantine, within the range currently used and well tolerated for the treatment of Alzheimer's disease, produce a protective effect in stroke. A coculture preparation exposed to modeled ischemia showed cell death associated with rapid glutamate rises and cytotoxic Ca2+ influx. Cell death was significantly enhanced in the presence of high memantine concentrations. However, low memantine concentrations significantly protected neurons and glia via excitotoxic cascade interruption. Mice were systemically administered a range of memantine doses (0.02, 0.2, 2, 10, and 20 mg/kg/day) starting 24 hours before 60 minutes reversible focal cerebral ischemia and continuing for a 48-hour recovery period. Low dose (0.2 mg/kg/day) memantine treatment significantly reduced lesion volume (by 30% to 50%) and improved behavioral outcomes in stroke lesions that had been separated into either small/striatal or large/striatocortical infarcts. However, higher doses of memantine (20 mg/kg/day) significantly increased injury. These results show that clinically established low doses of memantine should be considered for patients ‘at risk' of stroke, while higher doses are contraindicated. PMID:25407270

Whole-brain Irradiation Field Design: A Comparison of Parotid Dose.

PubMed

Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish; Saraf, Anurag; Tai, Cheng-Hung; Lapa, Matthew E; Andrew, Jacquelyn I S; Tiwari, Akhil; Saadatmand, Heva J; Isaacson, Steven R; Cheng, Simon K; Wang, Tony J C

2017-01-01

Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: mean <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED 3 , the parotid doses were lower than BED 3 constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED 3 conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose constraint with BED 3 should be less than 32.83 Gy. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Whole-brain Irradiation Field Design: A Comparison of Parotid Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish

Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: meanmore » <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED{sub 3}, the parotid doses were lower than BED{sub 3} constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED{sub 3} conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose constraint with BED{sub 3} should be less than 32.83 Gy.« less

A comparison of the abilities of chlorpromazine and molindone to interact adversely with guanethidine.

PubMed

Gilder, D A; Fain, W; Simpson, L L

1976-08-01

Chlorpromazine and molindone were tested for their abilities to impair conditioned avoidance behavior of rats. Chlorpromazine was effective within the dose range of 0.3 to 7.0 mg/kg (ID50approximately 2.0 mg/kg); molindone was effective within the range of 0.3 to 5.0 mg/kg (ID50 approximately 0.6 mg/kg). Behaviorally relevant doses of chlorpromazine and molindone were then tested for their effects on blood pressure and on adrenergic mechanisms. When given intravenously to anesthetized, hypertensive animals, both drugs (1.0 mg/kg) produced significant but transient vasodepression. When given intraperitoneally to anesthetized or to conscious hypertensive rats, the drugs did not produce significant effects on blood pressure. Both drugs (1.0 mg/kg) blocked responses to an alpha agonist (methoxamine), but chlorpromazine was significantly more potent than molindone. In addition, chlorpromazine produced a dose-dependent (1.0-10.0 mg/kg) inhibition of 3H-l-norepinephrine uptake into heart, but molindone at the same doses produced no inhibition of uptake. In related experiments, it was found that guanethidine (50 mg/kg) was an effective agent for lowering blood pressure of hypertensive rats. When chlorpromazine (3-10 mg/kg) was administered concomitantly with guanethidine, the blood pressure lowering properties of guanethidine were diminished or abolished. When molindone (1-10 mg/kg) was administered concomitantly with guanethidine, there was no loss of blood pressure control. It is concluded that molindone is an important drug, because it is an antipsychotic agent that does not interact adversely with guanethidine.

Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.

PubMed

Provenzano, Robert; Besarab, Anatole; Wright, Steven; Dua, Sohan; Zeig, Steven; Nguyen, Peter; Poole, Lona; Saikali, Khalil G; Saha, Gopal; Hemmerich, Stefan; Szczech, Lynda; Yu, K H Peony; Neff, Thomas B

2016-06-01

Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. Short treatment duration and small sample size. In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Stomach Cancer Following Hodgkin Lymphoma, Testicular Cancer and Cervical Cancer: A Pooled Analysis of Three International Studies with a Focus on Radiation Effects.

PubMed

Gilbert, Ethel S; Curtis, Rochelle E; Hauptmann, Michael; Kleinerman, Ruth A; Lynch, Charles F; Stovall, Marilyn; Smith, Susan A; Weathers, Rita; Andersson, Michael; Dores, Graça M; Fraumeni, Joseph F; Fossa, Sophie D; Hall, Per; Hodgson, David C; Holowaty, Eric J; Joensuu, Heikki; Johannesen, Tom B; Langmark, Froydis; Kaijser, Magnus; Pukkala, Eero; Rajaraman, Preetha; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Aleman, Berthe M; Travis, Lois B; Morton, Lindsay M; van Leeuwen, Flora E

2017-02-01

To further understand the risk of stomach cancer after fractionated high-dose radiotherapy, we pooled individual-level data from three recent stomach cancer case-control studies. These studies were nested in cohorts of five-year survivors of first primary Hodgkin lymphoma (HL), testicular cancer (TC) or cervical cancer (CX) from seven countries. Detailed data were abstracted from patient records and radiation doses were reconstructed to the site of the stomach cancer for cases and to the corresponding sites for matched controls. Among 327 cases and 678 controls, mean doses to the stomach were 15.3 Gy, 24.7 Gy and 1.9 Gy, respectively, for Hodgkin lymphoma, testicular cancer and cervical cancer survivors, with an overall mean dose of 10.3 Gy. Risk increased with increasing radiation dose to the stomach cancer site (P < 0.001) with no evidence of nonlinearity or of a downturn at the highest doses (≥35 Gy). The pooled excess odds ratio per Gy (EOR/Gy) was 0.091 [95% confidence interval (CI): 0.036-0.20] with estimates of 0.049 (95% CI: 0.007-0.16) for Hodgkin lymphoma, 0.27 (95% CI: 0.054-1.44) for testicular cancer and 0.096 (95% CI: -0.002-0.39) for cervical cancer (P homogeneity = 0.25). The EOR/Gy increased with time since exposure (P trend = 0.004), with an EOR/Gy of 0.38 (95% CI: 0.12-1.04) for stomach cancer occurring ≥20 years postirradiation corresponding to odds ratios of 4.8 and 10.5 at radiation doses to the stomach of 10 and 25 Gy, respectively. Of 111 stomach cancers occurring ≥20 years after radiotherapy, 63.8 (57%) could be attributed to radiotherapy. Our findings differ from those based on Japanese atomic-bomb survivors, where the overall EOR/Gy was higher and where there was no evidence of an increase with time since exposure. By pooling data from three studies, we demonstrated a clear increase in stomach cancer risk over a wide range of doses from fractionated radiotherapy with the highest risks occurring many years after exposure. These findings highlight the need to directly evaluate the health effects of high-dose fractionated radiotherapy rather than relying on the data of persons exposed at low and moderate acute doses.

Efficacy comparison of scopolamine (SCP) and diazepam (DZ) against soman-induced lethality in guinea pigs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, L.W.; Gennings, C.; Carter, W.H.

1994-12-31

Diazepam (DZ) and scopolamine (SCP) are known to be beneficial when each is used in combination with atropine (AT) + oxime therapy against intoxication by soman, but the efficacy of each might be expected to vary with the dosage of AT. Thus, the therapeutic efficacy of SCP (5 doses; 0 - 0.86 mg/kg) versus DZ (5 doses; 0 - 5 mg/kg), when used in conjunction with AT (3 doses; 0.5 - S mg/kg) + 2-PAM (25 mg/kg) therapy, was tested in groups of pyridostigmine pretreated guinea pigs exposed to 1.6, 2.0, 2.5 or 3.2 LD5Os of soman. Response surface methodologymore » was employed to describe the relationship between lethality and the AT/DZ or AT/SCP dosages. Results show that within the indicated dose ranges used, the efficacy of SCP is not dependent on the presence of AT, whereas AT is needed for DZ to maintain the lowest probability of death. These findings suggest that in guinea pigs SCP could supplement AT or replace DZ as therapy against nerve agent intoxication.« less

Low dose anti-thymocyte globulin reduces chronic graft-versus-host disease incidence rates after matched unrelated donor transplantation.

PubMed

Tandra, Anand; Covut, Fahrettin; Cooper, Brenda; Creger, Richard; Brister, Lauren; McQuigg, Bernadette; Caimi, Paolo; Malek, Ehsan; Tomlinson, Ben; Lazarus, Hillard M; Otegbeye, Folashade; Kolk, Merle; de Lima, Marcos; Metheny, Leland

2017-12-04

Anti-thymocyte globulin (ATG) is often added to hematopoietic stem cell transplant conditioning regimens to prevent graft rejection and reduce graft-versus-host disease (GVHD). Doses used in retrospective and prospective clinical trials have ranged from 2.5 to 20 mg/kg with rates of grade II-IV acute GVHD and chronic GVHD up to 40 and 60%, respectively. We retrospectively compared outcomes in recipients of matched unrelated donor (MUD) grafts given low dose rabbit ATG IV 3 mg/kg (n = 52) versus recipients of matched related donor (MRD) grafts (n = 48) without ATG. One year cumulative incidence of chronic GVHD was 25.2% in the MUD group versus 33.3% in the MRD group (p = .5). One-year cumulative incidence of extensive chronic GVHD was 9.6% in the MUD group versus 26.6% in the MRD group (p = .042). Our analysis supports the use of low dose ATG in MUD transplantation as an effective therapy to prevent chronic GVHD.

Initial experience with the 3.3 Fr Mongoose® pigtail catheter for aortic angiography during patent ductus arteriosus closure in small patients.

PubMed

Hena, Zachary; Sutton, Nicole J; Gates, Gregory J; Taragin, Benjamin H; Pass, Robert H

2017-01-01

Smaller femoral arterial sheaths may be associated with fewer vascular complications. The 3.3 Fr Mongoose ® Pediavascular pigtail catheter is a catheter that allows higher flow rates, potentially resulting in improved angiographic quality. We reviewed our experience with this small catheter during patent ductus arteriosus (PDA) closure. Review of patients ≤20 kg in whom the Mongoose ® catheter was used during PDA closure from 12/13 to 4/15. Angiographic efficacy and procedural details were compared to ten 4 Fr catheter cases. Comparisons were performed using Mann-Whitney U-test; P < 0.05 was statistically significant. Twelve (9 female) patients were catheterized with a 3.3 Fr Mongoose ® . Median weight 10.5 kg (range 6.4-18.2), height 81 cm (range 37-111), and body surface area (BSA) 0.47 m 2 (range 0.33-0.75) were similar to ten patients (3 females) in the 4 Fr control group ( P = NS); median weight 9.9 kg (range 6-16.8), height 80 cm (range 64-102), and BSA 0.46 m2 (range 0.31-0.74). Angiographic quality was subjectively adequate with both with no difference in the median pixel density between the two techniques (3.3 Fr: 76.7 [range 33.5-90] and 4 Fr: [70; 38-102]; P = NS). Contrast used was similar between the groups (3.3 Fr: median 4.2 ml/kg and 4 Fr: 4.9 ml/kg; P = NS). Median radiation dose was similar in the two groups (3.3 Fr: 28.1 mGy [range 17.2-38] and 4 Fr: 38 mGy [range 20.4-58.5]; P = NS). All ducts were closed at latest follow-up ( P = NS). No complications were encountered. The 3.3 Fr Mongoose ® allowed similar angiography to the 4 Fr pigtail catheter, allowing safe and effective transcatheter PDA closure in small children.

Real-time dose adjustment using point-of-care platelet reactivity testing in a double-blind study of prasugrel in children with sickle cell anaemia.

PubMed

Jakubowski, Joseph A; Hoppe, Carolyn C; Zhou, Chunmei; Smith, Brendan E; Brown, Patricia B; Heath, Lori E; Inusa, Baba; Rees, David C; Small, David S; Gupta, Neehar; Yao, Suqin; Heeney, Matthew; Kanter, Julie

2017-02-28

Patients with sickle cell anaemia (SCA) have vaso-occlusive crises resulting from occlusive hypoxic-ischaemic injury. Prasugrel inhibits platelet activation and aggregation involved in SCA pathophysiology. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) was a phase 3, double-blind, randomised, placebo-controlled trial assessing prasugrel efficacy. DOVE sought to bring patients' P2Y12 reaction unit (PRU) value within a targeted range via prasugrel dose adjustments using encrypted VerifyNow P2Y12 ® (VN-P2Y12) point-of-care testing and an interactive voice-response system (IVRS). After PRU determination, randomised patients received 0.08 mg/kg/day prasugrel or placebo. Encrypted PRUs and IVRS provided double-blind dose adjustments to achieve a defined PRU target range of 136-231; placebo patients had mock titrations. Of 341 randomised patients, 166 placebo and 160 prasugrel patients reached the fully titrated dose (FTD). Most prasugrel patients (n=104, 65 %) remained on the initial 0.08 mg/kg dose; doses escalations occurred in 23 % of patients (n=36). Mean PRUs for the pharmacodynamic population at baseline were similar in the prasugrel (273 ± 44.9) and placebo groups (273 ± 51.7), with significant reductions in PRU (p<0.001) for prasugrel patients at the FTD and at 9 months. Concomitant use of hydroxyurea did not affect platelet reactivity at any time. The majority of prasugrel patients (n=135, 84.4 %) at the FTD were within the target range of 136-231 PRUs. Mean VN-P2Y12 percentage inhibition at baseline was similar in the prasugrel (2.8  ± 5.4 %) and placebo groups (2.0 ± 4.7 %); prasugrel patients had significant increases in inhibition (p<0.001) at FTD and at 9 months. Patients with higher PRU values at baseline required higher prasugrel doses to bring PRU within the prespecified range. DOVE is the first study to successfully employ double-blind, real-time, encrypted, point-of-care platelet testing and IVRS to dose-adjust antiplatelet therapy to a targeted range of platelet inhibition.

Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI.

PubMed

Gong, Enhao; Pauly, John M; Wintermark, Max; Zaharchuk, Greg

2018-02-13

There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. Retrospective, crossover. Sixty patients receiving clinically indicated contrast-enhanced brain MRI. 3D T 1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma. For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images. Results were assessed using paired t-tests and noninferiority tests. The proposed deep learning method yielded significant (n = 50, P < 0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n = 20, P = 0.003) and contrast enhancement (n = 20, P < 0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n = 20, P = 0.083) and contrast enhancement (n = 20, P = 0.068). Slightly better (n = 20, P = 0.039) motion-artifact suppression was noted in the synthesized images. The noninferiority test rejects the inferiority of the synthesized to true full-dose images for image quality (95% CI: -14-9%), artifacts suppression (95% CI: -5-20%), and contrast enhancement (95% CI: -13-6%). With the proposed deep learning method, gadolinium dose can be reduced 10-fold while preserving contrast information and avoiding significant image quality degradation. 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

The dose-response of Harshaw TLD-700H.

PubMed

Velbeck, K J; Luo, L Z; Ramlo, M J; Rotunda, J E

2006-01-01

Harshaw TLD-700H (7LiF:Mg,Cu,P) was previously characterised for low- to high-dose ranges from 1 microGy to 20 Gy. This paper describes the studies and results of dose-response and linearity at much higher doses. TLD-700H is a near perfect dosimetric material with near tissue equivalence, flat energy response, and the ability to measure beta, gamma and X rays. These new results extend the applicability of Harshaw TLD-700H into more dosimetric measurement environments. The simple glow curve structure provides insignificant fade, eliminating special oven preparation methods experienced by other materials. The work presented in this paper quantifies the performance of Harshaw TLD-700H in extended ranges.

Assessment of target dose delivery in anal cancer using in vivo thermoluminescent dosimetry.

PubMed

Weber, D C; Nouet, P; Kurtz, J M; Allal, A S

2001-04-01

To measure anal dose during external beam radiotherapy (EBRT) using in vivo dosimetry, to study the difference of measured from prescribed dose values, and to evaluate possible associations of such differences with acute and late skin/mucosal toxicity and anorectal function. Thirty-one patients with localized anal carcinoma underwent in vivo measurements during the first EBRT session. Themoluminescent dosimeters (TLD) were placed at the center of the anal verge according to a localization protocol. No bolus was used. Patients received a median dose of 39.6 Gy (range: 36-45 Gy) by anteroposterior opposed AP/PA pelvic fields with 6 or 18 MV photons, followed by a median boost dose of 20 Gy (range: 13-24 Gy). Concomitant chemotherapy (CCT), consisting of 1-2 cycles of continuous infusion 5-fluorouracil (5-FU) and bolus mitomycin-C (MMC), was usually administered during the first weeks of the pelvic and boost EBRT courses. Acute and late skin/mucosal reactions were recorded according to the Radiation Therapy Oncology Group (RTOG) toxicity scale. Anal sphincter function was assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) scale. TLD anal doses differed by a mean of 5.8% (SD: 5.8) in comparison to the central axis prescribed dose. Differences of at least 10% and at least 15% were observed in eight (26%) and three (9.7%) patients, respectively. TLD doses did not significantly correlate with acute or late grade 2-3 skin or mucosal toxicity. However, patients having good-fair MSKCC anal function had a significantly greater mean difference in anal TLD dose (10.5%, SD: 5.9) than patients having excellent function (3.8%, SD: 4.6) (P = 0.004). Prescribed dose values, length of follow-up, and age at diagnosis did not correlate with late sphincter function. These data show that AP/PA fields using megavoltage photons deliver adequate dose to the anal verge. However, in about one quarter of patients treated with this technique the anal dose varied from the prescribed dose by at least 10%. The observed correlation of TLD values and late sphincter function suggests that direct measurement of the dose delivered to the anal verge might be clinically relevant.

Dosimetric characteristics of a PIN diode for radiotherapy application.

PubMed

Kumar, R; Sharma, S D; Philomina, A; Topkar, A

2014-08-01

The PIN diode developed by Bhabha Atomic Research Centre (BARC) was modified for its use as a dosimeter in radiation therapy. For this purpose the diode was mounted on a printed circuit board (PCB) and provided with necessary connections so that its response against irradiation can be recorded by a standard radiotherapy electrometer. The dosimetric characteristics of the diode were studied in Co-60 gamma rays as well as high energy X-rays. The measured sensitivity of this PIN diode is 4 nC/cGy which is about ten times higher than some commercial diode dosimeters. The leakage current from the diode is 0.04 nA. The response of the PIN diode is linear in the range of 20-1000 cGy which covers the full range of radiation dose encountered in radiotherapy treatments. The non-linearity of the diode response is 3.5% at 20 cGy and it is less than 1.5% at higher dose values. Its repeatability is within 0.5%. The angular response variation is about 5.6% within 6608 with respect to normal beam incidence. The response of the PIN diode at 6 and 18 MV X-rays varies within 2% with respect to its response at Co-60 gamma rays. The source to surface distance (SSD) dependence of the PIN diode was studied for Co-60 beam. It was found that the response of the diode decreases almost linearly relative to given dose for beams with constant collimator setting but increasing SSD (decreasing dose-rate). Within this study the diode response varied by about 2.5% between the maximum and minimum SSD. The dose-rate dependence of the PIN diode for 6 and 15 MV-rays was studied. The variation in response of diode for both energies in the studied dose range is less than 1%. The field size dependence of the PIN diode response is within 1% with respect to the response of ionisation chamber. These studies indicate that the characteristics of the PIN diode are suitable for use in radiotherapy dosimetry.

Kodak EDR2 film for patient skin dose assessment in cardiac catheterization procedures.

PubMed

Morrell, R E; Rogers, A T

2006-07-01

Patient skin doses were measured using Kodak EDR2 film for 20 coronary angiography (CA) and 32 percutaneous transluminal coronary angioplasty (PTCA) procedures. For CA, all skin doses were well below 1 Gy. However, 23% of PTCA patients received skin doses of 1 Gy or more. Dose-area product (DAP) was also recorded and was found to be an inadequate indicator of maximum skin dose. Practical compliance with ICRP recommendations requires a robust method for skin dosimetry that is more accurate than DAP and is applicable over a wider dose range than EDR2 film.

Evaluation and comparison of absorbed dose for electron beams by LiF and diamond dosimeters

NASA Astrophysics Data System (ADS)

Mosia, G. J.; Chamberlain, A. C.

2007-09-01

The absorbed dose response of LiF and diamond thermoluminescent dosimeters (TLDs), calibrated in 60Co γ-rays, has been determined using the MCNP4B Monte Carlo code system in mono-energetic megavoltage electron beams from 5 to 20 MeV. Evaluation of the dose responses was done against the dose responses of published works by other investigators. Dose responses of both dosimeters were compared to establish if any relation exists between them. The dosimeters were irradiated in a water phantom with the centre of their top surfaces (0.32×0.32 cm 2), placed at dmax perpendicular to the radiation beam on the central axis. For LiF TLD, dose responses ranged from 0.945±0.017 to 0.997±0.011. For the diamond TLD, the dose response ranged from 0.940±0.017 to 1.018±0.011. To correct for dose responses by both dosimeters, energy correction factors were generated from dose response results of both TLDs. For LiF TLD, these correction factors ranged from 1.003 up to 1.058 and for diamond TLD the factors ranged from 0.982 up to 1.064. The results show that diamond TLDs can be used in the place of the well-established LiF TLDs and that Monte Carlo code systems can be used in dose determinations for radiotherapy treatment planning.

Dosimetric Predictors of Symptomatic Cardiac Events after Conventional-Dose Chemoradiation Therapy for Inoperable Non-Small Cell Lung Cancer.

PubMed

Yegya-Raman, Nikhil; Wang, Kyle; Kim, Sinae; Reyhan, Meral; Deek, Matthew P; Sayan, Mutlay; Li, Diana; Patel, Malini; Malhotra, Jyoti; Aisner, Joseph; Marks, Lawrence B; Jabbour, Salma K

2018-06-05

We hypothesized that higher cardiac doses correlates with clinically significant cardiotoxicity after standard-dose chemoradiation therapy (CRT) (∼60 Gy) for inoperable non-small cell lung cancer (NSCLC). We retrospectively reviewed the records of 140 patients with inoperable NSCLC treated with concurrent CRT from 2007-2015. Extracted data included baseline cardiac status, dosimetric parameters to the whole heart (WH) and cardiac substructures, and the development of post-CRT symptomatic cardiac events (acute coronary syndrome [ACS], arrhythmia, pericardial effusion, pericarditis, and congestive heart failure [CHF]). Competing risks analysis was used to estimate time to cardiac events. Median follow-up was 47.4 months. Median radiation therapy dose was 61.2 Gy (interquartile range, 60-66 Gy). Forty patients (28.6%) developed 47 symptomatic cardiac events at a median of 15.3 months to first event. On multivariate analysis, higher WH doses and baseline cardiac status were associated with an increased risk of symptomatic cardiac events. The 4-year cumulative incidence of symptomatic cardiac events was 48.6% versus 18.5% for mean WH dose ≥ 20 Gy versus < 20 Gy, respectively (p = 0.0002). Doses to the WH, ventricles, and left anterior descending artery were associated with ACS/CHF, whereas doses to the WH and atria were not associated with supraventricular arrhythmias. Symptomatic cardiac events (p = 0.0001) were independently associated with death. Incidental cardiac irradiation was associated with subsequent symptomatic cardiac events, particularly ACS/CHF, and symptomatic cardiac events were associated with inferior survival. These results support the minimization of cardiac doses among patients with inoperable NSCLC receiving standard-dose CRT. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

A Microdose PET Study of the Safety, Immunogenicity, Biodistribution, and Radiation Dosimetry of 18F-FB-A20FMDV2 for Imaging the Integrin αvβ6.

PubMed

Keat, Nicholas; Kenny, Julia; Chen, Keguan; Onega, Mayca; Garman, Nadia; Slack, Robert J; Parker, Christine A; Lumbers, R Thomas; Hallett, Will; Saleem, Azeem; Passchier, Jan; Lukey, Pauline T

2018-06-01

The α v β 6 integrin is involved in the pathogenesis of cancer and fibrosis. A radiolabeled 20-amino-acid α v β 6 -binding peptide, derived from the foot and mouth virus (NAVPNLRGDLQVLAQKVART [A20FMDV2]), has been developed to image α v β 6 levels preclinically. This study was designed to translate these findings into a clinical PET imaging protocol to measure the expression of α v β 6 in humans. Methods: Preclinical toxicology was undertaken, and a direct immunoassay was developed for 4-fluorobenzamide (FB)-A20FMDV2. Four healthy human subjects (2 male and 2 female) received a single microdose of 18 F-FB-A20FMDV2 followed by a multibed PET scan of the whole body over more than 3 h. Results: There were no findings in the preclinical toxicology assessments, and no anti-A20FMDV2 antibodies were detected before or after dosing with the PET ligand. The mean and SD of the administered mass of 18 F-FB-A20FMDV2 was 8.7 ± 4.4 μg (range, 2.7-13.0 μg). The mean administered activity was 124 ± 20 MBq (range, 98-145 MBq). There were no adverse or clinically detectable pharmacologic effects in any of the subjects. No significant changes in vital signs, laboratory study results, or electrocardiography results were observed. Uptake of radioactivity was observed in the thyroid, salivary glands, liver, stomach wall, spleen, kidneys, ureters, and bladder. Time-activity curves indicated that the highest activity was in the bladder content, followed by the kidneys, small intestine, stomach, liver, spleen, thyroid, and gallbladder. The largest component of the residence times was the voided urine, followed by muscle, bladder, and liver. Using the mean residence time over all subjects as input to OLINDA/EXM, the effective dose was determined to be 0.0217 mSv/MBq; using residence times from single subjects gave an SD of 0.0020 mSv/MBq from the mean. The critical organ was the urinary bladder, with an absorbed dose of 0.18 mGy/MBq. Conclusion: 18 F-FB-A20FMDV2 successfully passed toxicology criteria, showed no adverse effects in this first-in-humans study, and has an effective dose that enables multiple scans in a single subject. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Degradation and decoloration of textiles wastewater by electron beam irradiation: Effect of energy, current and absorbed dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakar, Khomsaton Abu; Zulkafli,; Hashim, Siti A'aisah

2014-09-03

In this study, electron beam accelerator (EB) was used to treat textiles wastewater from Rawang Industrial Park, Selangor. The objectives were to determine effective energy, beam current and absorbed dose required for decoloration and degradation of the textiles effluent. The textiles effluent was irradiated in a batch with various energy of 1MeV to 3MeV at constant beam current of 30mA. It was observed that removal of color and COD increases with higher beam energy. The EB energy of 1MeV effectively to removed 58% color and 19% COD. For textile effluent sample irradiated at fix energy of 1MeV and 3Mev butmore » at different beam current 10mA, 20mA and 30mA. It was observed that removal of color and COD increases with the increased of beam current at each energy. However removal of color was significantly better at 1Mev as compared to 3Mev. In the case of textiles effluent, irradiated at doses of 17, 20,25,30, 35, 100 and 200kGy using 30 kW power of EB (1Mev, 30mA), results shows removal of BOD{sub 5}, COD and color were in the range 9%-33%, 14%-38% and 43%-78% respectively.« less

Comparison of Biological Effectiveness of Carbon-Ion Beams in Japan and Germany

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uzawa, Akiko; Ando, Koichi; Koike, Sachiko

2009-04-01

Purpose: To compare the biological effectiveness of 290 MeV/amu carbon-ion beams in Chiba, Japan and in Darmstadt, Germany, given that different methods for beam delivery are used for each. Methods and Materials: Murine small intestine and human salivary gland tumor (HSG) cells exponentially growing in vitro were irradiated with 6-cm width of spread-out Bragg peaks (SOBPs) adjusted to achieve nearly identical beam depth-dose profiles at the Heavy-Ion Medical Accelerator in Chiba, and the SchwerIonen Synchrotron in Darmstadt. Cell kill efficiencies of carbon ions were measured by colony formation for HSG cells and jejunum crypts survival in mice. Cobalt-60 {gamma} raysmore » were used as the reference radiation. Isoeffective doses at given survivals were used for relative biological effectiveness (RBE) calculations and interinstitutional comparisons. Results: Isoeffective D{sub 10} doses (mean {+-} standard deviation) of HSG cells ranged from 2.37 {+-} 0.14 Gy to 3.47 {+-} 0.19 Gy for Chiba and from 2.31 {+-} 0.11 Gy to 3.66 {+-} 0.17 Gy for Darmstadt. Isoeffective D{sub 10} doses of gut crypts after single doses ranged from 8.25 {+-} 0.17 Gy to 10.32 {+-} 0.14 Gy for Chiba and from 8.27 {+-} 0.10 Gy to 10.27 {+-} 0.27 Gy for Darmstadt, whereas isoeffective D{sub 30} doses after three fractionated doses were 9.89 {+-} 0.17 Gy through 13.70 {+-} 0.54 Gy and 10.14 {+-} 0.20 Gy through 13.30 {+-} 0.41 Gy for Chiba and Darmstadt, respectively. Overall difference of RBE between the two facilities was 0-5% or 3-7% for gut crypt survival or HSG cell kill, respectively. Conclusion: The carbon-ion beams at the National Institute of Radiological Sciences in Chiba, Japan and the Gesellschaft fuer Schwerionenforschung in Darmstadt, Germany are biologically identical after single and daily fractionated irradiation.« less

The threshold of hypothyroidism after radiation therapy for head and neck cancer: a retrospective analysis of 116 cases.

PubMed

Fujiwara, Masayuki; Kamikonya, Norihiko; Odawara, Soichi; Suzuki, Hitomi; Niwa, Yasue; Takada, Yasuhiro; Doi, Hiroshi; Terada, Tomonori; Uwa, Nobuhiro; Sagawa, Kosuke; Hirota, Shozo

2015-05-01

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose-volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1-62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Impact of treatment planning with deformable image registration on dose distribution for carbon-ion beam lung treatment using a fixed irradiation port and rotating couch.

PubMed

Kumagai, M; Mori, S; Yamamoto, N

2015-06-01

When using a fixed irradiation port, treatment couch rotation is necessary to increase beam angle selection. We evaluated dose variations associated with positional morphological changes to organs. We retrospectively chose the data sets of ten patients with lung cancer who underwent respiratory-gated CT at three different couch rotation angles (0°, 20° and -20°). The respective CT data sets are referred to as CT0, CT20 and CT-20. Three treatment plans were generated as follows: in Plan 1, all compensating bolus designs and dose distributions were calculated using CT0. To evaluate the rotation effect without considering morphology changes, in Plan 2, the compensating boli designed using CT0 were applied to the CT±20 images. Plan 3 involved compensating boli designed using the CT±20 images. The accumulated dose distributions were calculated using deformable image registration (DIR). A sufficient prescribed dose was calculated for the planning target volume (PTV) in Plan 1 [minimum dose received by a volume ≥95% (D95) > 95.8%]. By contrast, Plan 2 showed degraded dose conformation to the PTV (D95 > 90%) owing to mismatch of the bolus design to the morphological positional changes in the respective CT. The dose assessment results of Plan 3 were very close to those of Plan 1. Dose distribution is significantly affected by whether or not positional organ morphology changes are factored into dose planning. In treatment planning using multiple CT scans with different couch positions, it is mandatory to calculate the accumulated dose using DIR.

Studies on enhancing the keeping quality of peach ( Prunus persica Bausch) Cv. Elberta by gamma-irradiation

NASA Astrophysics Data System (ADS)

Hussain, P. R.; Meena, R. S.; Dar, M. A.; Wani, A. M.

2008-04-01

The effect of gamma-irradiation on keeping quality of peach fruit was studied. The fruit, after harvesting at proper maturity stage, was irradiated in the dose range of 1.0-2.0 kGy, stored under ambient (temp. 25±2 °C, RH 70%) and refrigerated (temp. 3±1 °C, RH 80%) conditions and evaluated periodically for firmness, total soluble solids (TSS), anthocyanins, water-soluble pectic fractions, loss in weight and decay percentage. The anthocyanin evaluation of the fruits revealed that irradiation enhanced the colour development under both the storage conditions. The gamma-irradiation dose range of 1.2-1.4 kGy proved effective in maintaining higher TSS concentration, reducing weight loss and significantly ( p⩽0.05) delaying the decaying of the fruit by 6 days under ambient conditions and by 20 days under refrigerated storage conditions.

Distribution of Absorbed Dose in Cone-Beam Breast Computed Tomography: A Phantom Study With Radiochromic Films

NASA Astrophysics Data System (ADS)

Russo, Paolo; Coppola, Teresa; Mettivier, Giovanni

2010-08-01

Cone-Beam Breast Computed Tomography (CBBCT) of the pendant breast with dedicated scanners is an experimental 3D X-ray imaging technique for breast cancer diagnosis under evaluation in comparison to conventional two-view 2-D mammography of the compressed breast. In CBBCT it is generally assumed that a more uniform distribution of the radiation dose to the breast volume can be obtained, with respect to mammography, at equal Mean Glandular Dose (MGD) levels. In fact, in CBBCT the X-ray beam rotates for 360 deg around the breast, while in each mammography view the breast is irradiated from one side only. Using a CBBCT laboratory scanner developed by our group, we have measured the distribution of the radiation dose in a hemi-ellipsoidal PMMA breast phantom of 14 cm diameter simulating the average uncompressed breast, using radiochromic films type XR-SP inserted at mid-plane in the phantom. The technique factors were 80 kVp (5.6 mm Al Half Value Layer), tube load in the range 23-100 mAs, for an air kerma at isocenter in the range 4.7-20 mGy, for a calculated MGD in the range 3.5-15 mGy for a 14 cm diameter breast of 50% glandularity. Results indicate that the dose decreases from the periphery to the center of the phantom, and that along a transverse profile, the relative dose variation Δ = ((edge-center)/center) is up to (25 ±4)% at a distance of 80 mm from the nipple. As for the relative dose variation along the phantom longitudinal axis, the maximum value at middle of the phantom measured is δ = ((nipple-chest wall)/chest wall) = -(15 ±4)%, indicating that the dose decreases from the chest wall toward the nipple. The values of the parameters Δ and δ depend also on the height of the X-ray tube focal spot with respect to the phantom vertex (nipple). Results are in rough agreement with similar previous determinations using thermoluminescence dosimeters.

Electron beam assisted synthesis of silver nanoparticle in chitosan stabilizer: Preparation, stability and inhibition of building fungi studies

NASA Astrophysics Data System (ADS)

Jannoo, Kanokwan; Teerapatsakul, Churapa; Punyanut, Adisak; Pasanphan, Wanvimol

2015-07-01

Silver nanoparticles (AgNPs) in chitosan (CS) stabilizer were successfully synthesized using electron beam irradiation. The effects of irradiation dose, molecular weight (MW) of CS stabilizer, concentration of AgNO3 precursor and addition of tert-butanol on AgNPs production were studied. The stability of the AgNPs under different temperatures and storage times were also investigated. The AgNPs formation in CS was observed using UV-vis, FT-IR and XRD. The characteristic surface plasmon resonance (SPR) of the obtained AgNPs was around 418 nm. The CS stabilizer and its MW, AgNO3 precursor and irradiation doses are important parameters for the synthesis of AgNPs. The optimum addition of 20% v/v tert-butanol could assist the formation of AgNPs. The AgNPs in CS stabilizer were stable over a period of one year when the samples were kept at 5 °C. The AgNPs observed from TEM images were spherical with an average particle size in the range of 5-20 nm depending on the irradiation doses. The AgNPs in CS solution effectively inhibited the growth of several fungi, i.e., Curvularia lunata, Trichoderma sp., Penicillium sp. and Aspergillus niger, which commonly found on the building surface.

TU-H-CAMPUS-TeP3-05: Evaluation of the Microscopic Dose Enhancement in the Nanoparticle-Enhanced Auger Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sung, W; Jung, S; Ye, S

Purpose: The aim of this study is to apply Monte Carlo simulations to investigate the nanoparticle dose enhancement for Auger therapy. Methods: Two nanoparticle fabrications were considered: nanoshell and nanosphere. In the first step, a single nanoparticle was irradiated with Auger emitters. The electrons were scored in a phase space at the outer surface of the nanoparticle with Geant4-Penelope. In the second step, the previously recorded phase space was used as a source and placed at the center of a cell-size water phantom. The nanoscale dose was evaluated in water around the nanoparticle with Geant4-DNA. The dose enhancement factor (DEF)more » is defined as the ratio of doses with and without nanoparticles. The nanoparticles were replaced by corresponding water nanoparticle with the same size and volume source which represents typical situation of Auger emitters without nanoparticle. Various sizes/materials of nanoparticles and isotopes were considered. Results: Nanoshell - Microscopic dose was increased up to 130% at 20 – 100 nm distances from the surface of Au-{sup 125}I nanoshell. However, dose at less than 20 nm distance was reduced due to absorbed low energy electrons in gold nanoshell. The amounts and regions of the dose enhancement were dependent on nanoshell size, materials, and isotopes. Nanosphere - The increased amounts of electrons up to 300% and reduced average energy with nanosphere were observed compared with water nanoparticle. We observed localized dose enhancement (up to a factor 3.6) in the immediate vicinity (< 50 nm) of Au-{sup 125} I nanosphere. The dose enhancement patterns vary according to nanosphere sizes and isotopes. Conclusion: We conclude that Auger therapy with nanoparticles can lead to change of electron energy spectrum and dose enhancements at certain range. The dose enhancement patterns vary according to nanoparticle sizes, materials, and isotopes. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP: Ministry of Science, ICT and Future Planning) (No. NRF-2013M2B2B1075776)« less

Skin dose in longitudinal and transverse linac-MRIs using Monte Carlo and realistic 3D MRI field models.

PubMed

Keyvanloo, A; Burke, B; Warkentin, B; Tadic, T; Rathee, S; Kirkby, C; Santos, D M; Fallone, B G

2012-10-01

The magnetic fields of linac-MR systems modify the path of contaminant electrons in photon beams, which alters patient skin dose. To accurately quantify the magnitude of changes in skin dose, the authors use Monte Carlo calculations that incorporate realistic 3D magnetic field models of longitudinal and transverse linac-MR systems. Finite element method (FEM) is used to generate complete 3D magnetic field maps for 0.56 T longitudinal and transverse linac-MR magnet assemblies, as well as for representative 0.5 and 1.0 T Helmholtz MRI systems. EGSnrc simulations implementing these 3D magnetic fields are performed. The geometry for the BEAMnrc simulations incorporates the Varian 600C 6 MV linac, magnet poles, the yoke, and the magnetic shields of the linac-MRIs. Resulting phase-space files are used to calculate the central axis percent depth-doses in a water phantom and 2D skin dose distributions for 70 μm entrance and exit layers using DOSXYZnrc. For comparison, skin doses are also calculated in the absence of magnetic field, and using a 1D magnetic field with an unrealistically large fringe field. The effects of photon field size, air gap (longitudinal configuration), and angle of obliquity (transverse configuration) are also investigated. Realistic modeling of the 3D magnetic fields shows that fringe fields decay rapidly and have a very small magnitude at the linac head. As a result, longitudinal linac-MR systems mostly confine contaminant electrons that are generated in the air gap and have an insignificant effect on electrons produced further upstream. The increase in the skin dose for the longitudinal configuration compared to the zero B-field case varies from ∼1% to ∼14% for air gaps of 5-31 cm, respectively. (All dose changes are reported as a % of D(max).) The increase is also field-size dependent, ranging from ∼3% at 20 × 20 cm(2) to ∼11% at 5 × 5 cm(2). The small changes in skin dose are in contrast to significant increases that are calculated for the unrealistic 1D magnetic field. For the transverse configuration, the entrance skin dose is equal or smaller than that of the zero B-field case for perpendicular beams. For a 10 × 10 cm(2) oblique beam the transverse magnetic field decreases the entry skin dose for oblique angles less than ±20° and increases it by no more than 10% for larger angles up to ±45°. The exit skin dose is increased by 42% for a 10 × 10 cm(2) perpendicular beam, but appreciably drops and approaches the zero B-field case for large oblique angles of incidence. For longitudinal linac-MR systems only a small increase in the entrance skin dose is predicted, due to the rapid decay of the realistic magnetic fringe fields. For transverse linac-MR systems, changes to the entrance skin dose are small for most scenarios. For the same geometry, on the exit side a fairly large increase is observed for perpendicular beams, but significantly drops for large oblique angles of incidence. The observed effects on skin dose are not expected to limit the application of linac-MR systems in either the longitudinal or transverse configuration.

The threshold of hypothyroidism after radiation therapy for head and neck cancer: a retrospective analysis of 116 cases

PubMed Central

Fujiwara, Masayuki; Kamikonya, Norihiko; Odawara, Soichi; Suzuki, Hitomi; Niwa, Yasue; Takada, Yasuhiro; Doi, Hiroshi; Terada, Tomonori; Uwa, Nobuhiro; Sagawa, Kosuke; Hirota, Shozo

2015-01-01

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose–volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1–62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers. PMID:25818629

Real-time in vivo dosimetry with MOSFET detectors in serial tomotherapy for head and neck cancer patients.

PubMed

Qi, Zhen-Yu; Deng, Xiao-Wu; Huang, Shao-Min; Shiu, Almon; Lerch, Michael; Metcalfe, Peter; Rosenfeld, Anatoly; Kron, Tomas

2011-08-01

A real-time dose verification method using a recently designed metal oxide semiconductor field effect transistor (MOSFET) dosimetry system was evaluated for quality assurance (QA) of intensity-modulated radiation therapy (IMRT). Following the investigation of key parameters that might affect the accuracy of MOSFET measurements (i.e., source surface distance [SSD], field size, beam incident angles and radiation energy spectrum), the feasibility of this detector in IMRT dose verification was demonstrated by comparison with ion chamber measurements taken in an IMRT QA phantom. Real-time in vivo measurements were also performed with the MOSFET system during serial tomotherapy treatments administered to 8 head and neck cancer patients. MOSFET sensitivity did not change with SSD. For field sizes smaller than 20 × 20 cm(2), MOFET sensitivity varied within 1.0%. The detector angular response was isotropic within 2% over 360°, and the observed sensitivity variation due to changes in the energy spectrum was negligible in 6-MV photons. MOSFET system measurements and ion chamber measurements agreed at all points in IMRT phantom plan verification, within 5%. The mean difference between 48 IMRT MOSFET-measured doses and calculated values in 8 patients was 3.33% and ranged from -2.20% to 7.89%. More than 90% of the total measurements had deviations of less than 5% from the planned doses. The MOSFET dosimetry system has been proven to be an effective tool in evaluating the actual dose within individual patients during IMRT treatment. Copyright © 2011 Elsevier Inc. All rights reserved.

SU-E-T-275: Dose Build Up and Bolusing Characteristics for Total Body Irradiation Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butson, M; Pope, D; Whitaker, M

2015-06-15

Purpose: Total Body Irradiation (TBI) treatments are mainly used in a preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. Our standard regimen is a 12 Gy / 6 fraction bi-daily technique. To evaluate the delivered dose homogeneity to the patient, EBT3 Gafchromic film is positioned at the head, neck, chest, pelvis and groin for all fractions. This work investigates and quantifies the build-up dose characteristics at TBI distances and requirements for in-vivo dosimetry bolusing. Methods: Percentage dose build up characteristics of photon beams have been investigated at large extended SSD’s using parallel plate ionisations chambers (Attix) and EBT3more » Gafchromic film. Measurements were made to open fields at different field sizes as well as large 40cm × 40cm fields with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point. Results: Percentage surface dose measured values for open fields at 300 cm SSD were found to range from 20 % up to 65.5 % for fields of 5 cm × 5 cm to 40 cm × 40 cm. With the introduction of 1cm Perspex scattering plates used in TBI treatments the surface dose values increased up to 83% to 90%, depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 3mm water equivalent bolus / scatter material should be placed over the EBT3 for accurate dose assessment for TBI treatments. Conclusion: Build up dose characteristics exist at long (300cm) SSD’s including treatments using Perspex scattering plates placed at various distances form the patient during TBI treatment. Top accurately assess the applied dose during treatment, in-vivo dosimeters such as Gafchromic EBT3 should have at least 3mm bolus / scatter material placed over them to measure actual applied doses.« less

Estimation of organ and effective doses from newborn radiography of the chest and abdomen.

PubMed

Ma, Hillgan; Elbakri, Idris A; Reed, Martin

2013-09-01

Neonatal intensive care patients undergo frequent chest and abdomen radiographic imaging. In this study, the organ doses and the effective dose resulting from combined chest-abdomen radiography of the newborn child are determined. These values are calculated using the Monte Carlo simulation software PCXCM 2.0 and compared with direct dose measurements obtained from thermoluminescent detectors (TLDs) in a physical phantom. The effective dose obtained from PCXMC is 21.2 ± 0.7 μSv and that obtained from TLD measurements is 22.0 ± 0.5 μSv. While the two methods are in close agreement with regard to the effective dose, there is a wide range of variation in organ doses, ranging from 85 % difference for the testes to 1.4 % for the lungs. Large organ dose variations are attributed to organs at the edge of the field of view, or organs with large experimental error or simulation uncertainty. This study suggests that PCXMC can be used to estimate organ and effective doses for newborn patients.

SU-D-BRC-07: System Design for a 3D Volumetric Scintillation Detector Using SCMOS Cameras

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darne, C; Robertson, D; Alsanea, F

2016-06-15

Purpose: The purpose of this project is to build a volumetric scintillation detector for quantitative imaging of 3D dose distributions of proton beams accurately in near real-time. Methods: The liquid scintillator (LS) detector consists of a transparent acrylic tank (20×20×20 cm{sup 3}) filled with a liquid scintillator that when irradiated with protons generates scintillation light. To track rapid spatial and dose variations in spot scanning proton beams we used three scientific-complementary metal-oxide semiconductor (sCMOS) imagers (2560×2160 pixels). The cameras collect optical signal from three orthogonal projections. To reduce system footprint two mirrors oriented at 45° to the tank surfaces redirectmore » scintillation light to cameras for capturing top and right views. Selection of fixed focal length objective lenses for these cameras was based on their ability to provide large depth of field (DoF) and required field of view (FoV). Multiple cross-hairs imprinted on the tank surfaces allow for image corrections arising from camera perspective and refraction. Results: We determined that by setting sCMOS to 16-bit dynamic range, truncating its FoV (1100×1100 pixels) to image the entire volume of the LS detector, and using 5.6 msec integration time imaging rate can be ramped up to 88 frames per second (fps). 20 mm focal length lens provides a 20 cm imaging DoF and 0.24 mm/pixel resolution. Master-slave camera configuration enable the slaves to initiate image acquisition instantly (within 2 µsec) after receiving a trigger signal. A computer with 128 GB RAM was used for spooling images from the cameras and can sustain a maximum recording time of 2 min per camera at 75 fps. Conclusion: The three sCMOS cameras are capable of high speed imaging. They can therefore be used for quick, high-resolution, and precise mapping of dose distributions from scanned spot proton beams in three dimensions.« less

Control of acid and duodenogastroesophageal reflux (DGER) in patients with Barrett's esophagus.

PubMed

Yachimski, Patrick; Maqbool, Sabba; Bhat, Yasser M; Richter, Joel E; Falk, Gary W; Vaezi, Michael F

2015-08-01

Symptom eradication in patients with Barrett's esophagus (BE) does not guarantee control of acid or duodenogastroesophageal reflux (DGER). Continued reflux of acid and/or DGER may increase risk of neoplastic progression and may decrease the likelihood of columnar mucosa eradication after ablative therapy. To date, no study has addressed whether both complete acid and DGER control is possible in patients with BE. This prospective study was designed to assess the effect of escalating-dose proton pump inhibitor (PPI) therapy on esophageal acid and DGER. Patients with BE (≥3 cm in length) underwent simultaneous ambulatory prolonged pH and DGER monitoring after at least 1 week off PPI therapy followed by testing on therapy after 1 month of twice-daily rabeprazole (20 mg). In those with continued acid and/or DGER, the tests were repeated after 1 month of double-dose (40 mg twice daily) rabeprazole. The primary study outcome was normalization of both acid and DGER. Symptom severity was assessed on and off PPI therapy employing a four-point ordinal scale. A total of 29 patients with BE consented for pH monitoring, of whom 23 also consented for both pH and DGER monitoring off and on therapy (83% male; mean age 58 years; mean body mass index 29; mean Barrett's length 6.0 cm). Median (interquartile range) total % time pH <4 and bilirubin absorbance >0.14 off PPI therapy were 18.4 (11.7-20.0) and 9.7 (5.0-22.2), respectively. In addition, 26/29 (90%) had normalized acid and 18/23 (78%) had normalized DGER on rabeprazole 20 mg. Among those not achieving normalization on 20 mg twice daily, 3/3 (100%) had normalized acid and 4/5 (80%) had normalized DGER on rabeprazole 40 mg twice daily. All subjects had symptoms controlled on rabeprazole 20 mg twice daily. Univariate analysis found no predictor for normalization of physiologic parameters based on demographics. Symptom control does not guarantee normalization of acid and DGER at standard dose of twice-daily PPI therapy. Normalization of acid and DGER can be achieved in 79% of BE patients on rabeprazole 20 mg p.o. twice daily, and in the majority of the remainder at high-dose twice-daily PPI. In patients undergoing ablative therapy, pH or DGER monitoring may not be needed to ensure normalization of reflux if patients are treated with high-dose PPI therapy.

Pharmacologically active phenylpropanoids from Senra incana.

PubMed

Farah, M H; Samuelsson, G

1992-02-01

Coniferaldehyde, scopoletin, sinapaldehyde, and syringaldehyde were isolated from an aqueous extract of Senra incana. All four compounds inhibited prostaglandin synthetase in a dose-dependent way. Compared to aspirin, the potency of coniferaldehyde and scopoletin was about five times higher, whereas syringaldehyde and sinapaldehyde had about half the potency of this reference compound. On topical application, sinapaldehyde and scopoletin dose-dependently inhibited ethyl phenylpropiolate-induced edema of the rat ear. The active dose range was 1-10 micrograms/ear. Higher doses had a lower effect. Syringaldehyde was active in the range 20-100 micrograms/ear, whereas the effect of coniferaldehyde was inconclusive. Coniferaldehyde and sinapaldehyde inhibited electrically induced contractions of the guinea pig ileum in a dose-dependent way. Syringaldehyde showed a weak inhibition at a concentration of 550 microM.

Radon-222 from different sources of water and the assessment of health hazard.

PubMed

Ademola, Janet A; Ojeniran, Oluwaferanmi R

2017-02-01

Water samples collected from different sources were analysed for radon concentrations in order to evaluate the health effect associated with radon in water. The radon concentrations were in the range of 3.56-98.57, 0.88-25.49, 0.73-1.35 and 0.24-1.03 Bq.L -1 for borehole, well, packaged and utility water, respectively. Samples from boreholes had the highest radon concentrations with about 67% being higher than the threshold value of 11.1 Bq.L -1 recommended by the USEPA. The mean annual effective dose (AED) due to ingestion for adult, child and infant ranged from 8.71 × 10 -3 to 0.831 mSv.y -1 for the different sources. The mean AED calculated for consuming water from boreholes and wells for the three age groups were higher than the recommended reference dose level of 0.1 mSv.y -1 . The mean AED due to inhalation of radon in drinking water was negligible, ranging from 0.13 to 6.20 μSv.y -1 . The health burden associated with radon in water in the study is through ingestion of water directly from boreholes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, M; Pompos, A; Gu, X

Purpose: To characterize the dose distributions of Cyberknife and intensity-modulated-proton-therapy (IMPT). Methods: A total of 20 patients previously treated with Cyberknife were selected. The original planning-target-volume (PTV) was used in the ‘IMPT-ideal’ plan assuming a comparable image-guidance with Cyberknife. A 3mm expansion was made to create the proton-PTV for the ‘IMPT-3mm’ plan representing the current proton-therapy where a margin of 3mm is used to account for the inferior image-guidance. The proton range uncertainty was taken-care in beam-design by adding the proximal- and distal-margins (3%water-equivalent-depth+1mm) for both proton plans. The IMPT plans were generated to meet the same target coverage asmore » the Cyberknife-plans. The plan quality of IMPT-ideal and IMPT-3mm were compared to the Cyberknife-plan. To characterize plan quality, we defined the ratio(R) of volumes encompassed by the selected isodose surfaces for Cyberknife and IMPT plans (VCK/VIMPT). Comparisons were made for both Cyberknife versus IMPT-ideal and Cyberknife versusIMPT-3mm to further discuss the impact of setup error margins used in proton therapy and the correlation with target size and location. Results: IMPT-ideal plans yield comparable plan quality as CK plans and slightly better OAR sparing while the IMPT-3mm plan results in a higher dose to the OARs, especially for centralized tumors. Comparing to the IMPT-ideal plans, a slightly larger 80% (Ravg=1.05) dose cloud and significantly larger 50% (Ravg=1.3) and 20% (Ravg=1.60) dose clouds are seen in CK plans. However, the 3mm expansion results in a larger high and medium dose clouds in IMPT-3mm plans (Ravg=0.65 for 80%-isodose; Ravg=0.93 for 50%-isodose). The trend increases with the size of the target and the distance from the brainstem to the center of target. Conclusion: Cyberknife is more preferable for treating centralized targets and proton therapy is advantageous for the large and peripheral targets. Advanced image guidance would improve the efficacy of proton therapy for intracranial treatments.« less

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013.

PubMed

Taylor, Carolyn W; Wang, Zhe; Macaulay, Elizabeth; Jagsi, Reshma; Duane, Frances; Darby, Sarah C

2015-11-15

Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this "mean heart dose." In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28 countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose. Copyright © 2015 Elsevier Inc. All rights reserved.

FIRST EURADOS INTERCOMPARISON EXERCISE OF EYE LENS DOSEMETERS FOR MEDICAL APPLICATIONS.

PubMed

Clairand, I; Ginjaume, M; Vanhavere, F; Carinou, E; Daures, J; Denoziere, M; Silva, E H; Roig, M; Principi, S; Van Rycheghem, L

2016-09-01

In the context of the decrease in the eye lens dose limit for occupational exposure to 20 mSv per year stated by the recent revision of the European Basic Safety Standards Directive 2013/59/EURATOM, the European Radiation Dosimetry Group (EURADOS) has organised in 2014, for the first time, an intercomparison exercise for eye lens dosemeters. The main objective was to assess the capabilities of the passive eye lens dosemeters currently in use in Europe for occupational monitoring in medical fields. A total of 20 European individual monitoring services from 15 different countries have participated. The dosemeters provided by the participants were all composed of thermoluminescent detectors, of various types and designs. The irradiations were carried out with several photon fields chosen to cover the energy and angle ranges encountered in medical workplace. Participants were asked to report the doses in terms of Hp(3) using their routine protocol. The results provided by each participant were compared with the reference delivered doses. All the results were anonymously analysed. Results are globally satisfactory since, among the 20 participants, 17 were able to provide 90 % of their response in accordance with the ISO 14146 standard requirements. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Consolidative proton therapy after chemotherapy for patients with Hodgkin lymphoma.

PubMed

Hoppe, B S; Hill-Kayser, C E; Tseng, Y D; Flampouri, S; Elmongy, H M; Cahlon, O; Mendenhall, N P; Maity, A; McGee, L A; Plastaras, J P

2017-09-01

We investigated early outcomes for patients receiving chemotherapy followed by consolidative proton therapy (PT) for the treatment of Hodgkin lymphoma (HL). From June 2008 through August 2015, 138 patients with HL enrolled on either IRB-approved outcomes tracking protocols or registry studies received consolidative PT. Patients were excluded due to relapsed or refractory disease. Involved-site radiotherapy field designs were used for all patients. Pediatric patients received a median dose of 21 Gy(RBE) [range 15-36 Gy(RBE)]; adult patients received a median dose of 30.6 Gy(RBE) [range, 20-45 Gy(RBE)]. Patients receiving PT were young (median age, 20 years; range 6-57). Overall, 42% were pediatric (≤18 years) and 93% were under the age of 40 years. Thirty-eight percent of patients were male and 62% female. Stage distribution included 73% with I/II and 27% with III/IV disease. Patients predominantly had mediastinal involvement (96%) and bulky disease (57%), whereas 37% had B symptoms. The median follow-up was 32 months (range, 5-92 months). The 3-year relapse-free survival rate was 92% for all patients; it was 96% for adults and 87% for pediatric patients (P = 0.18). When evaluated by positron emission tomography/computed tomography scan response at the end of chemotherapy, patients with a partial response had worse 3-year progression-free survival compared with other patients (78% versus 94%; P = 0.0034). No grade 3 radiation-related toxicities have occurred to date. Consolidative PT following standard chemotherapy in HL is primarily used in young patients with mediastinal and bulky disease. Early relapse-free survival rates are similar to those reported with photon radiation treatment, and no early grade 3 toxicities have been observed. Continued follow-up to assess late effects is critical. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

The boron implantation in the varied zone MBE MCT epilayer

NASA Astrophysics Data System (ADS)

Voitsekhovskii, Alexander V.; Grigor'ev, Denis V.; Kokhanenko, Andrey P.; Korotaev, Alexander G.; Sidorov, Yuriy G.; Varavin, Vasiliy S.; Dvoretsky, Sergey A.; Mikhailov, Nicolay N.; Talipov, Niyaz Kh.

2005-09-01

In the paper experimental results on boron implantation of the CdxHg1-xTe epilayers with various composition near surface of the material are discussed. The electron concentration in the surface layer after irradiation vs irradiation dose and ion energy are investigated for range of doses 1011 - 3•1015 cm-2 and energies of 20 - 150 keV. Also the results of the electrical active defects distribution measurement, carried out by differential Hall method, after boron implantation are represented. Consideration of the received data shows, that composition gradient influence mainly on the various dynamics of accumulation of electric active radiation defects. The electric active defects distribution analysis shows, that the other factors are negligible.

Pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses.

PubMed

Tsujimura, Koji; Yamada, Masayuki; Nagata, Shun-ichi; Yamanaka, Takashi; Nemoto, Manabu; Kondo, Takashi; Kurosawa, Masahiko; Matsumura, Tomio

2010-03-01

We investigated the pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses. Following an oral dose of famciclovir at 20 mg/kg, maximum plasma concentrations of penciclovir occurred between 0.75 and 1.5 hr (mean 0.94 + or - 0.38 hr) after dosing and were in the range 2.22 to 3.56 microg/ml (mean 2.87 + or - 0.61 microg/ml). The concentrations of penciclovir declined in a biphasic manner after the peak concentration was attained. The mean half-life of the rapid elimination phase was 1.73 + or - 0.34 hr whereas that of the slow elimination phase was 34.34 + or - 13.93 hr. These pharmacokinetic profiles observed were similar to those of another antiherpesvirus drug, acyclovir, previously reported in horses following oral dosing of its prodrug valacyclovir.

Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis. Comparison of two dosage schedules of choline magnesium trisalicylate.

PubMed

Cassell, S; Furst, D; Dromgoole, S; Paulus, H

1979-04-01

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a ddecrease of 1 mg/dl in mean minimum concentration.

SU-F-T-635: Lung SBRT: Dosimetric and Treatment Time Comparison of Volumetric-Modulated Arc Therapy and Three-Dimensional Conformal Radiotherapy in Clinically Treated Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, J; Xu, Z; Baker, J

Purpose: To compare three-dimensional conformal radiotherapy (3D CRT) and volumetric-modulated arc therapy (VMAT) in lung stereotactic body radiation therapy (SBRT) Methods: A retrospective study of clinically treated lung SBRT cases treated between 2010 and 2015 at our hospital was performed. All treatment modalities were included in this evaluation (VMAT, 3D CRT, static IMRT, and dynamic conformal arc therapy). However, the majority of treatment modalities were either VMAT or 3D CRT. Treatment times of patients and dosimetric plan quality metrics were compared. Treatment times were calculated based on the time the therapist opened and closed the patient’s treatment plan. This treatmentmore » time closely approximates the utilization time of the treatment room. The dosimetric plan quality metrics evaluated include ICRU conformity index, the volume of 105% prescribed dose outside PTV, the ratio of volume of 50% prescribed dose to the volume of PTV, the percentage of maximum dose at 2 cm away from PTV to the prescribed dose, and the V20 (percentage of lung volume receiving 20 Gy or more). Results: Treatment time comparisons show that on average VMAT has shorter treatment times than 3D CRT. Dose conformity, defined by the ICRU conformity index, and high dose spillage, defined by the volume of 105% dose outside the PTV, is reduced when using VMAT compared to 3D CRT. V20 and intermediate dose spillage/fall-off metrics of VMAT and 3D are not significantly different. Conclusion: Clinically treated lung SBRT cases indicate VMAT is superior to 3D with regard to shorter treatment times, plan dose conformity, and plan high dose spillage.« less

SU-E-T-188: Commission of World 1st Commercial Compact PBS Proton System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, X; Patel, B; Song, X

2015-06-15

Purpose: ProteusONE is the 1st commercial compact PBS proton system with an upstream scanning gantry and C230 cyclotron. We commissioned XiO and Raystation TPS simultaneously. This is a summary of beam data collection, modeling, and verification and comparison without range shiter for this unique system with both TPS. Methods: Both Raystation and XiO requires the same measurements data: (i) integral depth dose(IDDs) of single central spot measured in water tank; (ii) absolute dose calibration measured at 2cm depth of water with mono-energetic 10×10 cm2 field with spot spacing 4mm, 1MU per spot; and (iii) beam spot characteristics in air atmore » 0cm and ± 20cm away from ISO. To verify the beam model for both TPS, same 15 cube plans were created to simulate different treatment sites, target volumes and positions. PDDs of each plan were measured using a Multi-layer Ionization Chamber(MLIC), absolute point dose verification were measured using PPC05 in water tank and patient-specific QA were measured using MatriXX PT, a 2D ion chamber array. Results: All the point dose measurements at midSOBP were within 2% for both XiO and Raystation. However, up to 5% deviations were observed in XiO’s plans at shallow depth while within 2% in Raystation plans. 100% of the ranges measured were within 1 mm with maximum deviation of 0.5 mm. 20 patient specific plan were generated and measured in 3 planes (distal, proximal and midSOBP) in Raystation. The average of gamma index is 98.7%±3% with minimum 94% Conclusions: Both TPS were successfully commissioned and can be safely deployed for clinical use for ProteusONE. Based on our clinical experience in PBS planning, user interface, function and workflow, we preferably use Raystation as our main clinical TPS. Gamma Index >95% at 3%/3 mm criteria is our institution action level for patient specific plan QAs.« less

Retrospective study of palliative radiotherapy in newly diagnosed head and neck carcinoma.

PubMed

Stevens, Christiaan M; Huang, Shao Hui; Fung, Sharon; Bayley, Andrew J; Cho, John B; Cummings, Bernard J; Dawson, Laura A; Hope, Andrew J; Kim, John J; O'Sullivan, Brian; Waldron, John N; Ringash, Jolie

2011-11-15

To examine the patterns of care, outcomes, and prognostic factors for patients with head-and-neck cancer (HNC) treated with palliative radiotherapy (RT). An institutional HNC anthology and electronic patient records were used to identify patients with previously untreated HNC of mucosal or salivary gland origin who underwent palliative RT at our institution between July 2003 and June 2008. Overall survival was determined from the start date of RT to either the date of death or the date of last follow-up for living patients. The data were censored if the subject was either lost to follow-up or had not been seen for follow-up at our institution for ≥4 months. We identified 148 eligible patients. The median age was 72 years (range, 19-94). Of the 148 patients, 12 had Stage II-III, 39 Stage IVA, 36 Stage IVB, and 54 Stage IVC; for 7 patients, the stage was unknown. Oropharyngeal primary cancer (40) was the most common primary site. The Eastern Cooperative Oncology Group performance status was 0 in 15, 1 in 69, 2 in 40, 3 in 19, and 4 in 5 patients. The Adult Co-morbidity Evaluation-27 scale was 0 in 33, 1 in 47, 2 in 44, and 3 in 21. The median radiation dose was 50 Gy (range, 2-70), the median fraction number was 20 (range, 1-40), and the median total treatment time (including breaks) was 29 days (range, 1-80). At analysis, 108 patients (73%) had died, 20 (13.5%) were alive, and 20 (13.5%) had been censored. The median follow-up was 4.8 months, and the median survival time was 5.2 months. Information on the treatment response was available for 103 patients (70%). On multivariate analysis, the radiation dose was an independent predictor of both overall survival (hazard ratio 0.97, 95% confidence interval 0.96-0.99, p <.01) and treatment response (odds ratio 1.05, 95% confidence interval 1.01-1.08, p <.01). For patients considered unsuitable for curative RT, the radiation dose might be an independent predictive factor for both overall survival and treatment response. Additional research is required to more effectively select those patients who might benefit from more aggressive treatment. Copyright © 2011 Elsevier Inc. All rights reserved.

Dose, image quality and spine modeling assessment of biplanar EOS micro-dose radiographs for the follow-up of in-brace adolescent idiopathic scoliosis patients.

PubMed

Morel, Baptiste; Moueddeb, Sonia; Blondiaux, Eleonore; Richard, Stephen; Bachy, Manon; Vialle, Raphael; Ducou Le Pointe, Hubert

2018-05-01

The aim of this study was to compare the radiation dose, image quality and 3D spine parameter measurements of EOS low-dose and micro-dose protocols for in-brace adolescent idiopathic scoliosis (AIS) patients. We prospectively included 25 consecutive patients (20 females, 5 males) followed for AIS and undergoing brace treatment. The mean age was 12 years (SD 2 years, range 8-15 years). For each patient, in-brace biplanar EOS radiographs were acquired in a standing position using both the conventional low-dose and micro-dose protocols. Dose area product (DAP) was systematically recorded. Diagnostic image quality was qualitatively assessed by two radiologists for visibility of anatomical structures. The reliability of 3D spine modeling between two operators was quantitatively evaluated for the most clinically relevant 3D radiological parameters using intraclass correlation coefficient (ICC). The mean DAP for the posteroanterior and lateral acquisitions was 300 ± 134 and 433 ± 181 mGy cm 2 for the low-dose radiographs, and 41 ± 19 and 81 ± 39 mGy cm 2 for micro-dose radiographs. Image quality was lower with the micro-dose protocol. The agreement was "good" to "very good" for all measured clinical parameters when comparing the low-dose and micro-dose protocols (ICC > 0.73). The micro-dose protocol substantially reduced the delivered dose (by a factor of 5-7 compared to the low-dose protocol) in braced children with AIS. Although image quality was reduced, the micro-dose protocol proved to be adapted to radiological follow-up, with adequate image quality and reliable clinical measurements. These slides can be retrieved under Electronic Supplementary Material.

The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study.

PubMed

Chasset, François; Arnaud, Laurent; Costedoat-Chalumeau, Nathalie; Zahr, Noel; Bessis, Didier; Francès, Camille

2016-04-01

Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. The main limitations of the study are its open-label design and the limited number of patients included. Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models.

PubMed

Penny, Melissa A; Verity, Robert; Bever, Caitlin A; Sauboin, Christophe; Galactionova, Katya; Flasche, Stefan; White, Michael T; Wenger, Edward A; Van de Velde, Nicolas; Pemberton-Ross, Peter; Griffin, Jamie T; Smith, Thomas A; Eckhoff, Philip A; Muhib, Farzana; Jit, Mark; Ghani, Azra C

2016-01-23

The phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings. We compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5-17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2-10 year olds (PfPR2-10; range 3-65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2-10 per dose. In regions with a PfPR2-10 of 10-65%, RTS,S/AS01 is predicted to avert a median of 93,940 (range 20,490-126,540) clinical cases and 394 (127-708) deaths for the three-dose schedule, or 116,480 (31,450-160,410) clinical cases and 484 (189-859) deaths for the four-dose schedule, per 100,000 fully vaccinated children. A positive impact is also predicted at a PfPR2-10 of 5-10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2-10 of 10-65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18-211) per clinical case averted and $80 (44-279) per DALY averted for the three-dose schedule, and of $25 (16-222) and $87 (48-244), respectively, for the four-dose schedule. Higher ICERs were estimated at low PfPR2-10 levels. We predict a significant public health impact and high cost-effectiveness of the RTS,S/AS01 vaccine across a wide range of settings. Decisions about implementation will need to consider levels of malaria burden, the cost-effectiveness and coverage of other malaria interventions, health priorities, financing, and the capacity of the health system to deliver the vaccine. PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO. Copyright © 2016 Penny et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models

PubMed Central

Penny, Melissa A; Verity, Robert; Bever, Caitlin A; Sauboin, Christophe; Galactionova, Katya; Flasche, Stefan; White, Michael T; Wenger, Edward A; Van de Velde, Nicolas; Pemberton-Ross, Peter; Griffin, Jamie T; Smith, Thomas A; Eckhoff, Philip A; Muhib, Farzana; Jit, Mark; Ghani, Azra C

2016-01-01

Summary Background The phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings. Methods We compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5–17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2–10 year olds (PfPR2–10; range 3–65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2–10 per dose. Findings In regions with a PfPR2–10 of 10–65%, RTS,S/AS01 is predicted to avert a median of 93 940 (range 20 490–126 540) clinical cases and 394 (127–708) deaths for the three-dose schedule, or 116 480 (31 450–160 410) clinical cases and 484 (189–859) deaths for the four-dose schedule, per 100 000 fully vaccinated children. A positive impact is also predicted at a PfPR2–10 of 5–10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2–10 of 10–65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18–211) per clinical case averted and $80 (44–279) per DALY averted for the three-dose schedule, and of $25 (16–222) and $87 (48–244), respectively, for the four-dose schedule. Higher ICERs were estimated at low PfPR2–10 levels. Interpretation We predict a significant public health impact and high cost-effectiveness of the RTS,S/AS01 vaccine across a wide range of settings. Decisions about implementation will need to consider levels of malaria burden, the cost-effectiveness and coverage of other malaria interventions, health priorities, financing, and the capacity of the health system to deliver the vaccine. Funding PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO. PMID:26549466

[Pharmacokinetics and clinical efficacy of flomoxef in neonates].

PubMed

Azagami, S; Isohata, E; Takeda, S; Kin, Y; Oikawa, T; Osano, M; Shiro, H

1991-11-01

Clinical pharmacology and efficacy of flomoxef (FMOX) in neonates were investigated. And the following results were obtained. 1. Mean serum concentrations of FMOX at 30 minutes after administration were 24.3 micrograms/ml, 47.6 micrograms/ml, and 85.8 micrograms/ml at doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg administered, respectively. 2. Mean serum half-lives of FMOX were 3.4 hours in 0-3 day-old neonates, and 2.6 hours in 4 day-old or older subjects. 3. A dose response was evident among different dose groups given 10 mg/kg, 20 mg/kg, and 40 mg/kg. 4. Urinary recovery rates of FMOX in the first 6 hours after administration ranged between 12.8 and 51.1%. 5. FMOX was effective in 7 out of 8 cases in which causative pathogens were identified. 6. Diarrhea was observed in 1 case as a side effect of the drug, but the symptom was relieved soon after the completion of the treatment. There was no case in which any abnormal laboratory results were observed. 7. FMOX has a broad spectrum of activities against Gram-positive and Gram-negative aerobes and anaerobes. It is stable against most of beta-lactamases. It was demonstrated to be highly effective in our study, and yet without any serious side effects. FMOX is therefore considered to be one of the useful agents of the first choice for the treatment of bacterial infections such as sepsis and urinary tract infections in neonates and infants.

Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network Study GU14-206.

PubMed

Adra, N; Einhorn, L H; Althouse, S K; Ammakkanavar, N R; Musapatika, D; Albany, C; Vaughn, D; Hanna, N H

2018-01-01

Despite remarkable results with salvage standard-dose or high-dose chemotherapy ∼15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Single arm phase II trial investigating pembrolizumab 200 mg i.v. Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age ≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at least one salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary end point was overall response rate using immune-related response criteria. Simon two-stage design with type I error 20% and power 80% was utilized. Twelve male patients were enrolled. Median age was 38 years. All patients had nonseminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range 1-32, 760) and hCG 4 (range 0.6-37, 096). Six patients had late relapse (>2 years). Median number of previous chemotherapy regimens was 3. Six patients received prior high-dose chemotherapy. Two patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range 1-8). There were six grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. Two patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining. This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT. NCT02499952. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Escitalopram dose-response revisited: an alternative psychometric approach to evaluate clinical effects of escitalopram compared to citalopram and placebo in patients with major depression.

PubMed

Bech, Per; Tanghøj, Per; Cialdella, Philippe; Andersen, Henning Friis; Pedersen, Anders Gersel

2004-09-01

In continuation of a previous psychometric analysis of dose-response data for citalopram in depression, the corresponding study data for escitalopram is of interest, since escitalopram is the active enantiomer of citalopram and because citalopram was used as the active control. Revisiting those corresponding data, the psychometric properties of the Montgomery-Asberg Depression Scale (MADRS) and the Hamilton Depression Scale (HAMD) were investigated by focusing on the unidimensional HAMD6 and MADRS6. Effect sizes were calculated and compared for two dosages of escitalopram (10 mg and 20 mg daily) and between each of these two dosages and 40 mg citalopram daily. The results showed that the three depression scales MADRS6, MADRS10 and HAMD6 were psychometrically acceptable (coefficient of homogeneity of 0.40 or higher). In the severely depressed patients (MADRS10> or =30) a rather clear dose-response relationship for escitalopram was seen on all three scales after 6 and 8 wk of therapy. Thus, the effect size for 10 mg escitalopram ranged from 0.28 to 0.38 while the effect sizes for 20 mg escitalopram ranged from 0.57 to 0.77. This difference was statistically significant (p<0.01). The effect size for 40 mg citalopram ranged from 0.36 to 0.47, which is within the range found for 40 mg citalopram in our previous dose-response analysis of citalopram after 6 wk of therapy. The numerically largest difference between 20 mg escitalopram and 40 mg citalopram was seen after 8 wk of therapy for MADRS10 (effect size 0.71 vs. 0.37). An item analysis identified 'suicidal thoughts' to be the most discriminating item in this respect. These results for the severely depressed patients were confirmed by the patients self-reported quality of life evaluation. When all included patients were analysed, however, no clear dose-response relationship was seen. In conclusion, a dose-response relationship for escitalopram was seen in the severely depressed patients on all outcome scales after 6 and 8 wk of treatment. After 8 wk of treatment 20 mg escitalopram was superior to 40 mg citalopram, but not after 2 wk of treatment.

A Long-Acting Human Growth Hormone With Delayed Clearance (VRS-317): Results of a Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Growth Hormone–Deficient Adults

PubMed Central

Yuen, Kevin C. J.; Conway, Gerard S.; Popovic, Vera; Merriam, George R.; Bailey, Timothy; Hamrahian, Amir H.; Biller, Beverly M. K.; Kipnes, Mark; Moore, Jerome A.; Humphriss, Eric; Cleland, Jeffrey L.

2013-01-01

Background: Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes. Objectives: This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317. Design: This was a randomized, double-blind, placebo-controlled, single ascending dose study. Patients: Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo). Setting: The study was conducted in 17 adult endocrinology centers in North America and Europe. Main Outcome Measures: Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed. Results: At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3–5.0 μg/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between −1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed. Conclusions: The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing. PMID:23585663

A novel toxic alkaloid from poison hemlock (Conium maculatum L., Apiaceae): identification, synthesis and antinociceptive activity.

PubMed

Radulović, Niko; Dorđević, Nevenka; Denić, Marija; Pinheiro, Mariana Martins Gomes; Fernandes, Patricia Dias; Boylan, Fabio

2012-02-01

2-Pentylpiperidine, named conmaculatin, a novel volatile alkaloid related to coniine was identified from the renowned toxic weed Conium maculatum L. (Apiaceae). The structure of conmaculatin was corroborated by synthesis (8 steps starting from cyclohexanol, overall yield 12%). Conmaculatin's strong peripheral and central antinociceptive activity in mice was observed in a narrow dose range (10-20mg/kg). It was found to be lethal in doses higher than 20mg/kg. Copyright © 2011 Elsevier Ltd. All rights reserved.

SU-E-T-196: Comparative Analysis of Surface Dose Measurements Using MOSFET Detector and Dose Predicted by Eclipse - AAA with Varying Dose Calculation Grid Size

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badkul, R; Nejaiman, S; Pokhrel, D

2015-06-15

Purpose: Skin dose can be the limiting factor and fairly common reason to interrupt the treatment, especially for treating head-and-neck with Intensity-modulated-radiation-therapy(IMRT) or Volumetrically-modulated - arc-therapy (VMAT) and breast with tangentially-directed-beams. Aim of this study was to investigate accuracy of near-surface dose predicted by Eclipse treatment-planning-system (TPS) using Anisotropic-Analytic Algorithm (AAA)with varying calculation grid-size and comparing with metal-oxide-semiconductor-field-effect-transistors(MOSFETs)measurements for a range of clinical-conditions (open-field,dynamic-wedge, physical-wedge, IMRT,VMAT). Methods: QUASAR™-Body-Phantom was used in this study with oval curved-surfaces to mimic breast, chest wall and head-and-neck sites.A CT-scan was obtained with five radio-opaque markers(ROM) placed on the surface of phantom to mimic themore » range of incident angles for measurements and dose prediction using 2mm slice thickness.At each ROM, small structure(1mmx2mm) were contoured to obtain mean-doses from TPS.Calculations were performed for open-field,dynamic-wedge,physical-wedge,IMRT and VMAT using Varian-21EX,6&15MV photons using twogrid-sizes:2.5mm and 1mm.Calibration checks were performed to ensure that MOSFETs response were within ±5%.Surface-doses were measured at five locations and compared with TPS calculations. Results: For 6MV: 2.5mm grid-size,mean calculated doses(MCD)were higher by 10%(±7.6),10%(±7.6),20%(±8.5),40%(±7.5),30%(±6.9) and for 1mm grid-size MCD were higher by 0%(±5.7),0%(±4.2),0%(±5.5),1.2%(±5.0),1.1% (±7.8) for open-field,dynamic-wedge,physical-wedge,IMRT,VMAT respectively.For 15MV: 2.5mm grid-size,MCD were higher by 30%(±14.6),30%(±14.6),30%(±14.0),40%(±11.0),30%(±3.5)and for 1mm grid-size MCD were higher by 10% (±10.6), 10%(±9.8),10%(±8.0),30%(±7.8),10%(±3.8) for open-field, dynamic-wedge, physical-wedge, IMRT, VMAT respectively.For 6MV, 86% and 56% of all measured values agreed better than ±20% for 1mm and 2.5mm grid-sizes respectively. For 18MV, 56% and 18% of all measured-values agreed better than ±20% for 1mm and 2.5mm grid-sizes respectively. Conclusion: Reliable Skin-dose calculations by TPS can be very difficult due to steep dose-gradient and inaccurate beam-modelling in buildup region.Our results showed that Eclipse over-estimates surface-dose.Impact of grid-size is also significant,surface-dose increased up to 40% from 1mm to 2.5mm,however, 1mm calculated-values closely agrees with measurements. Due to large uncertnities in skin-dose predictions from TPS, outmost caution must be exercised when skin dose is evaluated,a sufficiently smaller grid-size(1mm)can improve the accuracy and MOSFETs can be used for verification.« less

High Dose Cytosine Arabinoside in the consolidation of adult acute myeloid leukemia.

PubMed

Rahman, M H; Khan, M A; Islam, M S; Afrose, S; Ara, T

2012-04-01

This interventional study was done to evaluate the duration of remission with High Dose Cytosine Arabinoside (Ara-C) as post-remission chemotherapy in the consolidation of adult acute myeloid leukemia. A total of 32 patients were included in this study. Among them, 19 were male and 13 were female and the age of the patients ranges from 15-60 years. We use High Dose Cytosine Arabinoside 1.5-2.5 g/m2 i.v, 12 hourly, over 2-3 hours on day 1, 3 and 5 in a 28 days cycle. This study was done during the period of April 2007 to March 2009 in the department of hematology, Dhaka Medical College & Hospital. History, clinical features and laboratory investigations were included. Among 32 patients, 5 patients (15.6%) received one cycle, 20 patients (62.5%) received two cycles and 7 patients (21.9%) received three cycles. The mean ± SD duration of remission (disease free survival) was 5.20 ± 3.83 months who received one cycle, 9.55 ± 3.30 months and 10.71 ± 1.70 months who received two cycles and three cycles respectively. The adverse effects of the therapy were neutropenia and neutropenic fever, purpuric rash, gum bleeding, mucositis and peripheral neuropathy. The supportive materials needed were antibiotics (both prophylactic and treatment) 86.13%, blood and blood products 51.7% and G-CSF 14.9% patients of all cycles. High Dose Ara-C (HiDAC) is a safe and cost effective consolidation treatment for AML patients in complete remission. This therapy merits multi-center control study to define its efficacy and cost-effectiveness in contrast to our socio-economic condition.

Urethral Pain Among Prostate Cancer Survivors 1 to 14 Years After Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pettersson, Niclas, E-mail: niclas.pettersson@vgregion.se; Olsson, Caroline; Tucker, Susan L.

Purpose: To investigate how treatment-related and non-treatment-related factors impact urethral pain among long-term prostate cancer survivors. Methods and Materials: Men treated for prostate cancer with radiation therapy at the Sahlgrenska University Hospital in Goeteborg, Sweden from 1993 to 2006 were approached with a study-specific postal questionnaire addressing symptoms after treatment, including urethral burning pain during urination (n=985). The men had received primary or salvage external-beam radiation therapy (EBRT) or EBRT in combination with brachytherapy (BT). Prescribed doses were commonly 70 Gy in 2.0-Gy fractions for primary and salvage EBRT and 50 Gy plus 2 Multiplication-Sign 10.0 Gy for EBRT +more » BT. Prostatic urethral doses were assessed from treatment records. We also recruited 350 non-pelvic-irradiated, population-based controls matched for age and residency to provide symptom background rates. Results: Of the treated men, 16% (137 of 863) reported urethral pain, compared with 11% (27 of 242) of the controls. The median time to follow-up was 5.2 years (range, 1.1-14.3 years). Prostatic urethral doses were similar to prescription doses for EBRT and 100% to 115% for BT. Fractionation-corrected dose and time to follow-up affected the occurrence of the symptom. For a follow-up {>=}3 years, 19% of men (52 of 268) within the 70-Gy EBRT + BT group reported pain, compared with 10% of men (23 of 222) treated with 70 Gy primary EBRT (prevalence ratio 1.9; 95% confidence interval 1.2-3.0). Of the men treated with salvage EBRT, 10% (20 of 197) reported urethral pain. Conclusions: Survivors treated with EBRT + BT had a higher risk for urethral pain compared with those treated with EBRT. The symptom prevalence decreased with longer time to follow-up. We found a relationship between fractionation-corrected urethral dose and pain. Among long-term prostate cancer survivors, the occurrence of pain was not increased above the background rate for prostatic urethral doses up to 70 Gy{sub 3}.« less

Adrenal hormones in rats before and after stress-experience: effects of ipsapirone.

PubMed

Korte, S M; Bouws, G A; Bohus, B

1992-06-01

The present study was designed to investigate the effects of the anxiolytic 5-HT1A receptor agonist ipsapirone on the hormonal responses in rats under nonstress and stress conditions by means of repeated blood sampling through an intracardiac catheter. Ipsapirone was given in doses of 2.5, 5, 10, and 20 mg/kg (IP) under nonstress conditions in the home cages of the rats. Plasma corticosterone levels increased in a dose-dependent way in the dose range of 5 to 20 mg/kg, whereas the plasma catecholamines were only significantly increased with the highest dose of the drug. The effect of ipsapirone in control and in stressed rats was studied with the selected dose of 5 mg/kg. Conditioned fear of inescapable electric footshock (0.6 mA, AC for 3 s) given one day earlier was used as stressor. Surprisingly, ipsapirone potentiated the magnitude of the neuroendocrine responses. Rats receiving an inescapable footshock 1 day earlier showed a further elevated corticosterone response to the 5-HT1A receptor agonist ipsapirone even before exposing them to the conditioned stress situation. The present findings suggest that if an animal has no possibilities to escape or avoid a noxious event, functional hypersensitivity will develop in the serotonergic neuronal system, which is reflected in the increased responsiveness of the HPA axis to a 5-HT1A agonist challenge.

In vivo combination of misonidazole and the chemotherapeutic agent CCNU.

PubMed Central

Siemann, D. W.

1981-01-01

The response of intramuscularly growing KHT sarcomas to the chemotherapeutic agent (1-(2-cloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) alone or simultaneously with the chemical radio-sensitizer misonidazole (MISO) was assessed using either a tumour growth-delay assay or an in vivo-in vitro tumour-excision assay. Median tumour growth delay following the combination of 20 mg/kg CCNU and either 0.5 or 1.0 mg/g MISO was 19.5 and 21.5 days, compared to 10 days for this CCNU dose alone. A similar degree of enhanced tumour response by MISO (factor of approximately 2 in tumour growth delay) was seen in RIF-1 tumours treated with 20 mg/kg CCNU plus 1.0 mg/g MISO. Clonogenic cell-survival studies with KHT sarcomas demonstrated that MISO at doses of 0.25, 0.5 or 1.0 mg/g given simultaneously with a range of CCNU doses produced dose-modifying factors (DMFs) of 1.9, 2.1 and 2.4 respectively. Normal tissue toxicity assessed by an LD50/7 assay led to DMFs of 1.2 and 1.4 for CCNU doses combined with 0.5 and 1.0 mg/g MISO. Thus in this animal tumour model the combination of CCNU and MISO appears to lead to a potential gain by a factor of approximately 1.7. PMID:7225287

Determining organ dose conversion coefficients for external neutron irradiation by using a voxel mouse model

PubMed Central

Zhang, Xiaomin; Xie, Xiangdong; Qu, Decheng; Ning, Jing; Zhou, Hongmei; Pan, Jie; Yang, Guoshan

2016-01-01

A set of fluence-to-dose conversion coefficients has been calculated for neutrons with energies <20 MeV using a developed voxel mouse model and Monte Carlo N-particle code (MCNP), for the purpose of neutron radiation effect evaluation. The calculation used 37 monodirectional monoenergetic neutron beams in the energy range 10−9 MeV to 20 MeV, under five different source irradiation configurations: left lateral, right lateral, dorsal–ventral, ventral–dorsal, and isotropic. Neutron fluence-to-dose conversion coefficients for selected organs of the body were presented in the paper, and the effect of irradiation geometry conditions, neutron energy and the organ location on the organ dose was discussed. The results indicated that neutron dose conversion coefficients clearly show sensitivity to irradiation geometry at neutron energy below 1 MeV. PMID:26661852

Antimicrobial prophylaxis for major head and neck surgery in cancer patients: sulbactam-ampicillin versus clindamycin-amikacin.

PubMed

Phan, M; Van der Auwera, P; Andry, G; Aoun, M; Chantrain, G; Deraemaecker, R; Dor, P; Daneau, D; Ewalenko, P; Meunier, F

1992-09-01

A total of 99 patients with head and neck cancer who were to undergo surgery were randomized in a prospective comparative study of sulbactam-ampicillin (1:2 ratio; four doses of 3 g of ampicillin and 1.5 g of sulbactam intravenously [i.v.] every 6 h) versus clindamycin (four doses of 600 mg i.v. every 6 h)-amikacin (two doses of 500 mg i.v. every 12 h) as prophylaxis starting at the induction of anesthesia. The two groups of evaluable patients (43 in the clindamycin-amikacin treatment group and 42 in the sulbactam-ampicillin treatment group) were comparable as far as age (mean, 57 years; range, 21 to 84 years), sex ratio (71 males, 28 females), weight (mean, 66 kg; range, 40 to 69 kg), indication for surgery (first surgery, 48 patients; recurrence, 37 patients), previous anticancer treatment (surgery, radiation therapy, chemotherapy), type of surgery, and stage of cancer. The overall infection rate (wound, bacteremia, and bronchopneumonia) within 20 days after surgery was 20 patients in each group. Wound infections occurred in 14 (33%) sulbactam-ampicillin-treated patients and 9 (21%) clindamycin-amikacin-treated patients (P = 0.19; not significant). The rates of bacteremia were 2 and 4%, respectively. The rates of bronchopneumonia were 14.3 and 23.2%, respectively (P was not significant). Most infections were polymicrobial, but strict anaerobes were recovered only from patients who received sulbactam-ampicillin. Antimicrobial treatment was required within 20 days after surgery for 42% of the sulbactam-ampicillin-treated patients and 44% of the clindamycin-amikacin-treated patients. By comparison with previous studies, we observed a decreased efficacy of antimicrobial prophylaxis in patients with head and neck cancer undergoing surgery because of the increased proportion of patients who were at very high risk for infection (extensive excision and plastic reconstruction in patients with recurrent stage III and IV cancers) and because of the longer duration of surgery.

Antimicrobial prophylaxis for major head and neck surgery in cancer patients: sulbactam-ampicillin versus clindamycin-amikacin.

PubMed Central

Phan, M; Van der Auwera, P; Andry, G; Aoun, M; Chantrain, G; Deraemaecker, R; Dor, P; Daneau, D; Ewalenko, P; Meunier, F

1992-01-01

A total of 99 patients with head and neck cancer who were to undergo surgery were randomized in a prospective comparative study of sulbactam-ampicillin (1:2 ratio; four doses of 3 g of ampicillin and 1.5 g of sulbactam intravenously [i.v.] every 6 h) versus clindamycin (four doses of 600 mg i.v. every 6 h)-amikacin (two doses of 500 mg i.v. every 12 h) as prophylaxis starting at the induction of anesthesia. The two groups of evaluable patients (43 in the clindamycin-amikacin treatment group and 42 in the sulbactam-ampicillin treatment group) were comparable as far as age (mean, 57 years; range, 21 to 84 years), sex ratio (71 males, 28 females), weight (mean, 66 kg; range, 40 to 69 kg), indication for surgery (first surgery, 48 patients; recurrence, 37 patients), previous anticancer treatment (surgery, radiation therapy, chemotherapy), type of surgery, and stage of cancer. The overall infection rate (wound, bacteremia, and bronchopneumonia) within 20 days after surgery was 20 patients in each group. Wound infections occurred in 14 (33%) sulbactam-ampicillin-treated patients and 9 (21%) clindamycin-amikacin-treated patients (P = 0.19; not significant). The rates of bacteremia were 2 and 4%, respectively. The rates of bronchopneumonia were 14.3 and 23.2%, respectively (P was not significant). Most infections were polymicrobial, but strict anaerobes were recovered only from patients who received sulbactam-ampicillin. Antimicrobial treatment was required within 20 days after surgery for 42% of the sulbactam-ampicillin-treated patients and 44% of the clindamycin-amikacin-treated patients. By comparison with previous studies, we observed a decreased efficacy of antimicrobial prophylaxis in patients with head and neck cancer undergoing surgery because of the increased proportion of patients who were at very high risk for infection (extensive excision and plastic reconstruction in patients with recurrent stage III and IV cancers) and because of the longer duration of surgery. PMID:1416895

In vitro efficacy of synthetic skin repellent IR3535 on head lice (Pediculus capitis).

PubMed

Rupes, Vaclav; Vlckova, Jana; Kollarova, Helena; Horakova, Dagmar; Mazanek, Libor; Kensa, Michal

2013-10-01

In in vitro tests, skin repellent IR3535, applied in the form of the Diffusil H Prevental product in an aerosol bomb (active compound 20%), killed 100% of head lice (females and males) and nymphs 2 and 3, when directly sprayed at a dose of 0.94 mg of the active compound per square centimeter. Crawling lice exposed for 1 min on the filter paper impregnated by the same concentration showed no effort to suck blood 30 min after exposition. Twenty hours later, their mortality rate was 11 %. After the lice had been exposed for approximately 1 min (until they actively left the area) on 5 cm round areas of skin of test persons treated with the repellent at a mean total dose of 23.3 mg of active compound, they showed no effort to suck blood on the clean skin of other test person either immediately after exposure or 30 min later. Their mortality after 20 h ranged from 59 to 16%, depending on the time elapsed from skin treatment (10 min to 27 h).

Dosimetry of {sup 210}Po in humans, caribou, and wolves in northern Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, P.A.

1994-06-01

Effective doses from {sup 210}Po intake with caribou meat were determined for human residents in Baker Lake and Snowdrift in the Northwest Territories of Canada and compared to doses calculated from reported {sup 210}Po tissue activities in Alaskan and British residents. Effective doses were calculated to separate body tissues, using ICRP 60 human weighting factors and the ICRP 30 metabolic model for {sup 210}Po. Baker Lake and Alaskan effective doses were similar at 0.4 mSv y{sup {minus}1} and slightly higher than Snowdrift doses (0.3 mSv y{sup {minus}1}). Alaskan tissue activities indicated higher effective doses to liver, bone surfaces and redmore » marrow and lower doses to spleen than the {sup 210}Po metabolic model (ICRP 1979a) predicts. Effective doses to Baker Lake and Snowdrift caribou and wolves, calculated from tissue activities, ranged from 7-20 mSv y{sup {minus}1} using human weighting factors for comparison to human doses only. Effective doses to northern Canadians and wildlife were, respectively, 7-11% and 1.8-5 times an estimated human background of 4 mSv y{sup {minus}} from all sources. 51 refs., 2 figs., 9 tabs.« less

Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: a pharmacokinetic evaluation.

PubMed

Nielsen, Torben K; Højgaard, Martin; Andersen, Jon T; Poulsen, Henrik E; Lykkesfeldt, Jens; Mikines, Kári J

2015-04-01

Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high-dose IV AA. The purpose of this study was to assess the basic kinetic variables in human beings over a relevant AA dosing interval for proper design of future clinical trials. Ten patients with metastatic prostate cancer were treated for 4 weeks with fixed AA doses of 5, 30 and 60 g. AA was measured consecutively in plasma and indicated first-order elimination kinetics throughout the dosing range with supra-physiological concentrations. The target dose of 60 g AA IV produced a peak plasma AA concentration of 20.3 mM. Elimination half-life was 1.87 hr (mean, S.D. ± 0.40), volume of distribution 0.19 L/kg (S.D. ±0.05) and clearance rate 6.02 L/hr (100 mL/min). No differences in pharmacokinetic parameters were observed between weeks/doses. A relatively fast first-order elimination with half-life of about 2 hr makes it impossible to maintain AA concentrations in the potential cytotoxic range after infusion stop in prostate cancer patients with normal kidney function. We propose a regimen with a bolus loading followed by a maintenance infusion based on the calculated clearance. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poplawski, L; Li, T; Chino, J

Purpose: In brachytherapy, structures surrounding the target have the potential to move between treatments and receive unknown dose. Deformable image registration could overcome challenges through dose accumulation. This study uses two possible deformable dose summation techniques and compares the results to point dose summation currently performed in clinic. Methods: Data for ten patients treated with a Syed template was imported into the MIM software (Cleveland, OH). The deformable registration was applied to structures by masking other image data to a single intensity. The registration flow consisted of the following steps: 1) mask CTs so that each of the structures-of-interest hadmore » one unique intensity; 2) perform applicator — based rigid registration; 3) Perform deformable registration; 4) Refine registration by changing local alignments manually; 5) Repeat steps 1 to 3 until desired structure adequately deformed; 5) Transfer each deformed contours to the first CT. The deformed structure accuracy was determined by a dice similarity coefficient (DSC) comparison with the first fraction. Two dose summation techniques were investigated: a deformation and recalculation on the structure; and a dose deformation and accumulation method. Point doses were used as a comparison value. Results: The Syed deformations have DSC ranging from 0.53 to 0.97 and 0.75 and 0.95 for the bladder and rectum, respectively. For the bladder, contour deformation addition ranged from −34.8% to 0.98% and dose deformation accumulation ranged from −35% to 29.3% difference from clinical calculations. For the rectum, contour deformation addition ranged from −5.2% to 16.9% and the dose deformation accumulation ranged from −29.1% to 15.3% change. Conclusion: Deforming dose for summation leads to different volumetric doses than when dose is recalculated on deformed structures, raising concerns about the accuracy of the deformed dose. DSC alone cannot be used to establish the accuracy of a deformation for brachy dose summation purpose.« less

Further assessment of the clinically effective dose range of etoricoxib: a randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis.

PubMed

Greenwald, M; Peloso, P M; Mandel, D; Soto, O; Mehta, A; Frontera, N; Boice, J A; Zhan, X J; Curtis, S P

2011-10-01

To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA). RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences. Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p < 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p < 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0). The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients. Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.

Out-of-Field Dose Equivalents Delivered by Passively Scattered Therapeutic Proton Beams for Clinically Relevant Field Configurations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wroe, Andrew; Centre for Medical Radiation Physics, University of Wollongong, Wollongong; Clasie, Ben

2009-01-01

Purpose: Microdosimetric measurements were performed at Massachusetts General Hospital, Boston, MA, to assess the dose equivalent external to passively delivered proton fields for various clinical treatment scenarios. Methods and Materials: Treatment fields evaluated included a prostate cancer field, cranial and spinal medulloblastoma fields, ocular melanoma field, and a field for an intracranial stereotactic treatment. Measurements were completed with patient-specific configurations of clinically relevant treatment settings using a silicon-on-insulator microdosimeter placed on the surface of and at various depths within a homogeneous Lucite phantom. The dose equivalent and average quality factor were assessed as a function of both lateral displacement frommore » the treatment field edge and distance downstream of the beam's distal edge. Results: Dose-equivalent value range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral displacement) for the ocular melanoma field. Measurements of external field dose equivalent for the stereotactic field case showed differences as high as 50% depending on the modality of beam collimation. Average quality factors derived from this work ranged from 2-7, with the value dependent on the position within the phantom in relation to the primary beam. Conclusions: This work provides a valuable and clinically relevant comparison of the external field dose equivalents for various passively scattered proton treatment fields.« less

General radiographic attributes of optically stimulated luminescence dosimeters: A basic insight

NASA Astrophysics Data System (ADS)

Musa, Y.; Hashim, S.; Ghoshal, S. K.; Bradley, D. A.; Ahmad, N. E.; Karim, M. K. A.; Hashim, A.; Kadir, A. B. A.

2018-06-01

We report the ubiquitous radiographic characteristics of optically stimulated luminescence dosimeters (OSLD) so called nanoDot OSLDs (Landauer Inc., Glendwood, IL). The X-ray irradiations were performed in free air ambiance to inspect the repeatability, the reproducibility, the signal depletion, the element correction factors (ECFs), the dose response and the energy dependence. Repeatability of multiple readouts after single irradiation to 10 mGy revealed a coefficient of variation below 3%, while the reproducibility in repeated irradiation-readout-annealing cycles was above 2%. The OSL signal depletion for three nanoDots with simultaneous irradiation to 20 mGy and sequential readouts of 25 times displayed a consistent signal reduction ≈0.5% per readout with R2 values over 0.98. ECFs for individual OSLDs were varied from 0.97 to 1.03. In the entire dose range under 80 kV, a good linearity with an R2 exceeding 0.99 was achieved. Besides, the percentage difference between OSLD and ion-chamber dose was less than 5%, which was superior to TLD. The X-ray photon irradiated energy response factors (between 0.76 and 1.12) in the range of 40-150 kV (26.1-61.2 keV) exhibited significant energy dependence. Indeed, the nanoDot OSLDs disclosed good repeatability, reproducibility and linearity. The OSLDs measured doses were closer to ion-chamber doses than that of TLD. It can be further improved up to ≈3% by applying the individual dosimeter ECF. On top, the energy dependent uncertainties can be minimized using the energy correction factors. It is established that the studied nanoDot OSLDs are prospective for measuring entrance dose in general radiographic practices.

Pb low doses induced genotoxicity in Lactuca sativa plants.

PubMed

Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C

2017-03-01

Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L -1 . In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO 3 ) 2 up to 20 mg L -1 . The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L -1 significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L -1 and presence of micronuclei (MN) were detected for 20 mg L -1 . Also, cell cycle impairment was observed for doses as low as 0.05 mg L -1 and 0.5 mg L -1 (mostly G 2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matney, Jason; Park, Peter C.; The University of Texas Graduate School of Biomedical Sciences, Houston, Texas

Purpose: To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans; and to establish the relationship between the magnitude of tumor motion and the respiratory-induced dose difference for both modalities. Methods and Materials: In a randomized clinical trial comparing PSPT and IMRT, radiation therapy plans have been designed according to common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging from 3 to 17 mm. Image registration and dose accumulation were performed using grayscale-based deformable imagemore » registration algorithms. The dose–volume histogram (DVH) differences (4D-3D [3D = 3-dimensional]) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion. Results: The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19 of 20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the 2 modalities was not statistically significant (P<.05) for all dose–volume histogram indices (mean ± SD) except the lung V5 (PSPT: +1.1% ± 0.9%; IMRT: +0.4% ± 1.2%) and maximum cord dose (PSPT: +1.5 ± 2.9 Gy; IMRT: 0.0 ± 0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only 2 indices: dose to 95% planning target volume, and heterogeneity index. Conclusions: With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2 of 11 4D-3D indices (lung V5 and spinal cord maximum) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Because of the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential dosimetric error caused by breathing motion.« less

Radiosurgery for Para-IAC Meningiomas: The Effect of Radiation Dose to the Cochlea on Hearing Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Young-Hoon; Department of Neurosurgery, Seoul National University College of Medicine, Seoul; Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.kr

2012-11-01

Purpose: This study was performed to assess the radiosurgical results of meningiomas extending into the internal acoustic canal (para-IAC meningiomas), with a particular focus on the effect of radiation dose to the cochlea on hearing outcome. Methods and Materials: A total of 50 patients who underwent radiosurgery for para-IAC meningiomas between 1998 and 2009, which were followed for 2 years, were enrolled. The mean age was 55.8 years (range, 15-75). The mean tumor volume was 6.1 cm{sup 3} (range, 1.0-19.0), the mean tumor length in the IAC was 6.9 mm (range, 1.3-13.3), and the mean prescribed marginal dose was 13.1more » Gy (range, 10-15) at an isodose line of 50%. The mean follow-up duration was 46 months (range, 24-122). Results: Eight (16.0%) patients had nonserviceable hearing at the time of surgery. At the last follow-up, the tumor control rate was 94%; unchanged in 17 patients, decreased in 30 patients, and increased in 3 patients. Among 42 patients with serviceable hearing at the time of radiosurgery, it was preserved in 41 (97.6%) patients at the last follow-up. The maximal and mean radiation doses to the cochleae of these 41 patients were 5.8 Gy {+-} 0.3 (range, 3.1-11.5) and 4.3 Gy {+-} 0.2 (range, 2.2-7.5), respectively. The maximal dose to the cochlea of the patient who lost hearing after radiosurgery was 4.7 Gy. Conclusions: The radiation dose to the cochlea may have the minimal toxic effect on the hearing outcome in patients who undergo radiosurgery for para-IAC meningiomas.« less

Gamma ionization of Phagicola longa (Trematoda:Heterophyidae) in Mugilidae (pisces) in São Paulo, Brazil

NASA Astrophysics Data System (ADS)

Antunes, S. A.; Wiendl, F. M.; Almeida Dias, E. R.; Arthur, V.; Daniotti, C.

1993-07-01

The mullet (Mugilidae) is a fish caught in large quantities in brackish and marine waters of the southern Brazilian coast, which in consequence of its raw consumption as "sashimi", a typical Japanese dish, has led to ten cases of human infection by Phagicola longa in São Paulo, Brazil. The mullet acts as a second intermediate host for the parasite, as in human heterophysiasis in the Near and Far East. In order to control these infections under commercial storage conditions and in raw consumption, the radiolysis of P. longa was studied in three mullet species-the silver mullet ( Mugil curema), the grey mullet ( M. platanus) and the "paratipema" ( Mugil sp.) - subjected to ionization ranging from 1.0 to 10.0 kGy (2.21 kGy/h). It was observed that 1.0 and 2.0 kGy caused a motility decrease in silver mullet parasites from 100% to 15% and 17%, and that doses of 4.0 and 10.0 kGy caused metacercaria inviability. The parasite motility decreased in the grey mullet treated with doses of 2.0, 2.5, 3.0 and 3.5 kGy, from 56% to 31%, 9%, 18% and 5%, respectively, 4.0 kGy tending to be the control dose for P. longa. This dose also controls other metacercaria found in the "parati-pema", without changing the odor, color or appearance of the treated mullet.

Carcinogenesis From Inhaled (PuO2)-Pu-239 in Beagles: Evidence for Radiation Homeostasis at Low Doses?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, Darrell R.; Weller, Richard E.

From the early 1970s to the late 1980s, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium (239PuO2, 238PuO2, and 239Pu[NO3]4) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study is to reassess the dose-response relationship for lung cancer induction in the 239PuO2 dogs compared to controls, with particular focus on the dose-response at low lung doses. A 239PuO2 aerosol (2.3 μm AMAD, 1.9 μm GSD) was administered to six groups of 20 young (18-month old) beagle dogs (10 males and 10more » females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 ± 48 Bq (3.5 ± 1.3 nCi), corresponding to 1 Bq g-1 lung tissue (0.029 ± 0.001 nCi g-1. Groups 2 through 6 received initial lung depositions (mean values) of 760, 2724, 10345, 37900, and 200000 Bq (22, 79, 300, 1100, and 5800 nCi) 239PuO2, respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, epidermoid carcinoma) and radiation pneumonitis (highest exposures group) was observed in dogs exposed to 239PuO2. Calculated lung doses ranged from a few cGy in early-sacrificed dogs to 7764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. Lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 ± 7.6 cGy), and only one lung tumor was observed in 10 dogs with lung doses ranging from 27 to 48 cGy (mean 37.5 ± 10.9 cGy). By least-squares analysis, a quadratic function represented the overall dose-response (n = 137, r = 0.96) with no dose threshold. Reducing this function to three linear dose-response components, risk coefficients were calculated for each. The incidence of lung tumors at zero dose was significantly greater than the incidence at low dose (at the p ≤ 0.053 confidence level), suggesting a protective effect (radiation homeostasis) of alpha-particle radiation from 239PuO2. If a threshold for lung cancer incidence exists, it will be observed in the range 15 to 40 cGy.« less

Magnetic fields are causing small, but significant changes of the radiochromic EBT3 film response to 6 MV photons

NASA Astrophysics Data System (ADS)

Delfs, Björn; Schoenfeld, Andreas A.; Poppinga, Daniela; Kapsch, Ralf-Peter; Jiang, Ping; Harder, Dietrich; Poppe, Björn; Khee Looe, Hui

2018-02-01

The optical density (OD) of EBT3 radiochromic films (Ashland Specialty Ingredients, Bridgewater, NJ, USA) exposed to absorbed doses to water up to D  =  20 Gy in magnetic fields of B  =  0.35 and 1.42 T was measured in the three colour channels of an Epson Expression 10000XL flatbed scanner. A 7 cm wide water phantom with fixed film holder was placed between the pole shoes of a constant-current electromagnet with variable field strength and was irradiated by a 6 MV photon beam whose axis was directed at right angles with the field lines. The doses at the film position at water depth 5 cm were measured with a calibrated ionization chamber when the magnet was switched off and were converted to the doses in presence of the magnetic field via the monitor units and by a Monte Carlo-calculated correction accounting for the slight change of the depth dose curves in magnetic fields. In the presence of the 0.35 and 1.42 T fields small negative changes of the OD values at given absorbed doses to water occurred and just significantly exceeded the uncertainty margin given by the stochastic and the uncorrected systematic deviations. This change can be described by a  +2.1% change of the dose values needed to produce a given optical density in the presence of a 1.42 T field. The thereby modified OD versus D function remained unchanged irrespective of whether the original short film side—the preference direction of the monomer crystals of the film—was directed parallel or orthogonal to the magnetic field. The ‘orientation effect’, the difference between the optical densities measured in the ‘portrait’ or ‘landscape’ film positions on the scanner bed caused by the reflection of polarised light in the scanner’s mirror system, remained unaltered after EBT3 film exposure in magnetic fields. An independent optical bench investigation of EBT3 films exposed to doses of 10 and 20 Gy at 0.35 and 1.42 T showed that the direction of the electric vector of polarised light experiencing the largest transmission through EBT3 films remained unaltered after film exposure in the magnetic fields. The observed small modification of the OD versus D curve of the radiochromic film EBT3 in the range up to 20 Gy and 1.42 T, hardly exceeding the experimental uncertainty margin, numerically confirms other recent studies on EBT3 film. A stronger magnetic field effect had been observed with the previous product EBT2 exposed to 60Co gamma radiation at 0.35 T.

Magnetic fields are causing small, but significant changes of the radiochromic EBT3 film response to 6 MV photons.

PubMed

Delfs, Björn; Schoenfeld, Andreas A; Poppinga, Daniela; Kapsch, Ralf-Peter; Jiang, Ping; Harder, Dietrich; Poppe, Björn; Looe, Hui Khee

2018-01-31

The optical density (OD) of EBT3 radiochromic films (Ashland Specialty Ingredients, Bridgewater, NJ, USA) exposed to absorbed doses to water up to D  =  20 Gy in magnetic fields of B  =  0.35 and 1.42 T was measured in the three colour channels of an Epson Expression 10000XL flatbed scanner. A 7 cm wide water phantom with fixed film holder was placed between the pole shoes of a constant-current electromagnet with variable field strength and was irradiated by a 6 MV photon beam whose axis was directed at right angles with the field lines. The doses at the film position at water depth 5 cm were measured with a calibrated ionization chamber when the magnet was switched off and were converted to the doses in presence of the magnetic field via the monitor units and by a Monte Carlo-calculated correction accounting for the slight change of the depth dose curves in magnetic fields. In the presence of the 0.35 and 1.42 T fields small negative changes of the OD values at given absorbed doses to water occurred and just significantly exceeded the uncertainty margin given by the stochastic and the uncorrected systematic deviations. This change can be described by a  +2.1% change of the dose values needed to produce a given optical density in the presence of a 1.42 T field. The thereby modified OD versus D function remained unchanged irrespective of whether the original short film side-the preference direction of the monomer crystals of the film-was directed parallel or orthogonal to the magnetic field. The 'orientation effect', the difference between the optical densities measured in the 'portrait' or 'landscape' film positions on the scanner bed caused by the reflection of polarised light in the scanner's mirror system, remained unaltered after EBT3 film exposure in magnetic fields. An independent optical bench investigation of EBT3 films exposed to doses of 10 and 20 Gy at 0.35 and 1.42 T showed that the direction of the electric vector of polarised light experiencing the largest transmission through EBT3 films remained unaltered after film exposure in the magnetic fields. The observed small modification of the OD versus D curve of the radiochromic film EBT3 in the range up to 20 Gy and 1.42 T, hardly exceeding the experimental uncertainty margin, numerically confirms other recent studies on EBT3 film. A stronger magnetic field effect had been observed with the previous product EBT2 exposed to 60 Co gamma radiation at 0.35 T.

Trivalent influenza vaccine-induced antibody response to circulating influenza a (H3N2) viruses in 2010/11 and 2011/12 seasons.

PubMed

Hiroi, Satoshi; Morikawa, Saeko; Nakata, Keiko; Maeda, Akiko; Kanno, Tsuneji; Irie, Shin; Ohfuji, Satoko; Hirota, Yoshio; Kase, Tetsuo

2015-01-01

To evaluate antibody response induced by trivalent inactivated influenza vaccine (TIV) against circulating influenza A (H3N2) strains in healthy adults during the 2010/11 and 2011/12 seasons, a hemagglutination-inhibition (HI) assay was utilized to calculate geometric mean antibody titer (GMT), seroprotection rate (post vaccination HI titers of ≥1 :40), and seroresponse rate (4-fold increase in antibody level). In the 2010/11 season, GMT increased 1.8- to 2.0-fold following the first dose of TIV against 3 circulating strains and 2.2-fold following the second compared to before vaccination. The seroresponse rate ranged from 22% to 26% following the first dose of TIV and from 31% to 33% following the second (n = 54 ). The seroprotection rate increased from a range of 6% to 13% to a range of 26% to 33% following the first dose of TIV and to a range of 37% to 42% following the second (n = 54 ). In the 2011/12 season, GMT increased 1.4-fold against A/Osaka/110/2011 and 1.8-fold against A/Osaka/5/2012. For A/Osaka/110/2011, the seroresponse rate was 29%, and the seroprotection rate increased from 26% to 55% following vaccination (n = 31 ). For A/Osaka/5/2012, the seroresponse rate was 26%, and the seroprotection rate increased from 68% to 84% following vaccination (n = 31 ). HI assays with reference antisera demonstrated that the strains in the 2011/12 season were antigenically distinct from vaccine strain (A/Victoria/210/2009). In conclusion, the vaccination increased the seroprotection rate against circulating H3N2 strains in the 2010/11 and 2011/12 seasons. Vaccination of TIV might have potential to induce reactive antibodies against antigenically distinct circulating H3N2 viruses.

Eye lens dose in interventional cardiology.

PubMed

Principi, S; Delgado Soler, C; Ginjaume, M; Beltran Vilagrasa, M; Rovira Escutia, J J; Duch, M A

2015-07-01

The ICRP has recently recommended reducing the occupational exposure dose limit for the lens of the eye to 20 mSv y(-1), averaged over a period of 5 y, with no year exceeding 50 mSv, instead of the current 150 mSv y(-1). This reduction will have important implications for interventional cardiology and radiology (IC/IR) personnel. In this work, lens dose received by a staff working in IC is studied in order to determine whether eye lens dose monitoring or/and additional radiological protection measures are required. Eye lens dose exposure was monitored in 10 physicians and 6 nurses. The major IC procedures performed were coronary angiography and percutaneous transluminal coronary angioplasty. The personnel were provided with two thermoluminescent dosemeters (TLDs): one calibrated in terms of Hp(3) located close to the left ear of the operator and a whole-body dosemeter calibrated in terms of Hp(10) and Hp(0.07) positioned on the lead apron. The estimated annual eye lens dose for physicians ranged between 8 and 60 mSv, for a workload of 200 procedures y(-1). Lower doses were collected for nurses, with estimated annual Hp(3) between 2 and 4 mSv y(-1). It was observed that for nurses the Hp(0.07) measurement on the lead apron is a good estimate of eye lens dose. This is not the case for physicians, where the influence of both the position and use of protective devices such as the ceiling shield is very important and produces large differences among doses both at the eyes and on the thorax. For physicians, a good correlation between Hp(3) and dose area product is shown. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bone cancer occurrence among beagles given 239Pu as young adults.

PubMed

Lloyd, R D; Taylor, G N; Angus, W; Bruenger, F W; Miller, S C

1993-01-01

The occurrence of skeletal malignancies has been documented among 234 young adult beagles given single intravenous injections of monomeric 239Pu citrate. Occurrence has also been documented among 132 comparable control group animals surviving the minimum latent time period of 2.79 y for radiation-induced bone cancer, who were maintained for lifespan observation. Injected amounts ranged from about 0.02-106 kBq kg-1 body mass with factors of 2 or 3 between dose levels. There were 84 radiographically apparent bone tumors in 76 plutonium-injected dogs and one tumor in a control group dog. Most of these were osteosarcomas except for seven chondrosarcomas, one liposarcoma, and one plasma cell myeloma of bone. The relationship between percent of dogs at any dose level with bone malignancy and average skeletal dose at the presumed time of tumor initiation of 1 y before death appeared to be linear below about 1.3 Gy average skeletal dose. The observed data can be approximated by the expression A = 0.76 + 75 D, where A = percent of dogs with bone cancer at any dose level, D = average skeletal dose in Gy (for doses up to 1.3 Gy) at tumor initiation, and 0.76 represents the percent tumor response in the control animals not given plutonium. Similar analysis of our corresponding data for beagles given 226Ra, excluding the two highest dose levels (approximately 100% occurrence), yielded the expression A = 0.76 + 4.7 D, where D = the average skeletal dose in Gy (for doses up to 20 Gy) at 1 y before death. The ratio of coefficients indicates the effectiveness for bone cancer induction of 239Pu relative to 226Ra, or [(75 +/- 22.5)(4.7 +/- 0.47)-1] = 16 +/- 5 for a single, brief intake of either nuclide into blood.

Experimental determination of particle range and dose distribution in thick targets through fragmentation reactions of stable heavy ions.

PubMed

Inaniwa, Taku; Kohno, Toshiyuki; Tomitani, Takehiro; Urakabe, Eriko; Sato, Shinji; Kanazawa, Mitsutaka; Kanai, Tatsuaki

2006-09-07

In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an ionization chamber. The good agreement between the derived and the measured distributions implies that the deposited dose distribution in a target can be estimated from the detected annihilation gamma-ray distribution with a positron camera.

Characterisation of a MOSFET-based detector for dose measurement under megavoltage electron beam radiotherapy

NASA Astrophysics Data System (ADS)

Jong, W. L.; Ung, N. M.; Tiong, A. H. L.; Rosenfeld, A. B.; Wong, J. H. D.

2018-03-01

The aim of this study is to investigate the fundamental dosimetric characteristics of the MOSkin detector for megavoltage electron beam dosimetry. The reproducibility, linearity, energy dependence, dose rate dependence, depth dose measurement, output factor measurement, and surface dose measurement under megavoltage electron beam were tested. The MOSkin detector showed excellent reproducibility (>98%) and linearity (R2= 1.00) up to 2000 cGy for 4-20 MeV electron beams. The MOSkin detector also showed minimal dose rate dependence (within ±3%) and energy dependence (within ±2%) over the clinical range of electron beams, except for an energy dependence at 4 MeV electron beam. An energy dependence correction factor of 1.075 is needed when the MOSkin detector is used for 4 MeV electron beam. The output factors measured by the MOSkin detector were within ±2% compared to those measured with the EBT3 film and CC13 chamber. The measured depth doses using the MOSkin detector agreed with those measured using the CC13 chamber, except at the build-up region due to the dose volume averaging effect of the CC13 chamber. For surface dose measurements, MOSkin measurements were in agreement within ±3% to those measured using EBT3 film. Measurements using the MOSkin detector were also compared to electron dose calculation algorithms namely the GGPB and eMC algorithms. Both algorithms were in agreement with measurements to within ±2% and ±4% for output factor (except for the 4 × 4 cm2 field size) and surface dose, respectively. With the uncertainties taken into account, the MOSkin detector was found to be a suitable detector for dose measurement under megavoltage electron beam. This has been demonstrated in the in vivo skin dose measurement on patients during electron boost to the breast tumour bed.

End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R: A paradigm shift in clinical decision making.

PubMed

Melani, Christopher; Advani, Ranjana; Roschewski, Mark; Walters, Kelsey M; Chen, Clara C; Baratto, Lucia; Ahlman, Mark A; Miljkovic, Milos D; Steinberg, Seth M; Lam, Jessica; Shovlin, Margaret; Dunleavy, Kieron; Pittaluga, Stefania; Jaffe, Elaine S; Wilson, Wyndham H

2018-05-10

Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow-up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPOCH-R without radiotherapy. End-of-treatment PET was performed in 80 patients, of whom 57 received 144 serial scans. One nuclear medicine physician from each institution blindly reviewed all scans from their respective institution. End-of-treatment PET was negative (Deauville 1-3) in 55 (69%) patients with one treatment failure (8-year event-free and overall survival of 96.0% and 97.7%). Among 25 (31%) patients with a positive (Deauville 4-5) end-of-treatment PET, there were 5 (20%) treatment failures (8-year event-free and overall survival of 71.1% and 84.3%). Linear regression analysis of serial scans showed a significant decrease in SUVmax in positive end-of-treatment PET non-progressors compared to an increase in treatment failures. Among 6 treatment failures, the median end-of-treatment SUVmax was 15.4 (range, 1.9-21.3) and 4 achieved long-term remission with salvage therapy. Virtually all patients with a negative end-of-treatment PET following dose-adjusted-EPOCH-R achieved durable remissions and should not receive radiotherapy. Among patients with a positive end-of-treatment PET, only 5/25 (20%) had treatment-failure. Serial PET imaging distinguished end-of-treatment PET positive patients without treatment failure, thereby reducing unnecessary radiotherapy by 80%, and should be considered in all patients with an initial positive PET following dose-adjusted-EPOCH-R (NCT00001337). Copyright © 2018, Ferrata Storti Foundation.

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.

1994-07-01

The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through amore » 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.« less

Occupational dose constraints in interventional cardiology procedures: the DIMOND approach

NASA Astrophysics Data System (ADS)

Tsapaki, Virginia; Kottou, Sophia; Vano, Eliseo; Komppa, Tuomo; Padovani, Renato; Dowling, Annita; Molfetas, Michael; Neofotistou, Vassiliki

2004-03-01

Radiation fields involved in angiographic suites are most uneven with intensity and gradient varying widely with projection geometry. The European Commission DIMOND III project addressed among others, the issues regarding optimization of staff doses with an attempt to propose preliminary occupational dose constraints. Two thermoluminescent dosemeters (TLD) were used to assess operators' extremity doses (left shoulder and left foot) during 20 coronary angiographies (CAs) and 20 percutaneous transluminal coronary angioplasties (PTCAs) in five European centres. X-ray equipment, radiation protection measures used and the dose delivered to the patient in terms of dose-area product (DAP) were recorded so as to subsequently associate them with operator's dose. The range of staff doses noted for the same TLD position, centre and procedure type emphasizes the importance of protective measures and technical characteristics of x-ray equipment. Correlation of patient's DAP with staff shoulder dose is moderate whereas correlation of patient's DAP with staff foot dose is poor in both CA and PTCA. Therefore, it is difficult to predict operator's dose from patient's DAP mainly due to the different use of protective measures. A preliminary occupational dose constraint value was defined by calculating cardiologists' annual effective dose and found to be 0.6 mSv.

Assessment of radiation doses from residential smoke detectors that contain americium-241

NASA Astrophysics Data System (ADS)

Odonnell, F. R.; Etnier, E. L.; Holton, G. A.; Travis, C. C.

1981-10-01

External dose equivalents and internal dose commitments were estimated for individuals and populations from annual distribution, use, and disposal of 10 million ionization chamber smoke detectors that contain 110 kBq americium-241 each. Under exposure scenarios developed for normal distribution, use, and disposal using the best available information, annual external dose equivalents to average individuals were estimated to range from 4 fSv to 20 nSv for total body and from 7 fSv to 40 nSv for bone. Internal dose commitments to individuals under post disposal scenarios were estimated to range from 0.006 to 80 micro-Sv (0.0006 to 8 mrem) to total body and from 0.06 to 800 micro-Sv to bone. The total collective dose (the sum of external dose equivalents and 50-year internal dose commitments) for all individuals involved with distribution, use, or disposal of 10 million smoke detectors was estimated to be about 0.38 person-Sv (38 person-rem) to total body and 00 ft squared.

Computational analysis of the dose rates at JSI TRIGA reactor irradiation facilities.

PubMed

Ambrožič, K; Žerovnik, G; Snoj, L

2017-12-01

The JSI TRIGA Mark II, IJS research reactor is equipped with numerous irradiation positions, where samples can be irradiated by neutrons and γ-rays. Irradiation position selection is based on its properties, such as physical size and accessibility, as well as neutron and γ-ray spectra, flux and dose intensities. This paper presents an overview on the neutron and γ-ray fluxes, spectra and dose intensities calculations using Monte Carlo MCNP software and ENDF/B-VII.0 nuclear data libraries. The dose-rates are presented in terms of ambient dose equivalents, air kerma, and silicon dose equivalent. At full reactor power the neutron ambient dose equivalent ranges from 5.5×10 3 Svh -1 to 6×10 6 Svh -1 , silicon dose equivalent from 6×10 2 Gy/h si to 3×10 5 Gy/h si , and neutron air kerma from 4.3×10 3 Gyh -1 to 2×10 5 Gyh -1 . Ratio of fast (1MeV

Phase I Trial of Aflibercept (VEGF Trap) with Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients with High-Grade Gliomas

PubMed Central

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred WK; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-01-01

Background Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor (PlGF), depleting circulating levels of these growth factors. Methods The Adult Brain Tumor Consortium (ABTC) conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed high-grade gliomas (HGG) with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Results Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4mg/kg every 2 weeks. Dose limiting toxicities (DLTs) at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. Conclusions This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4mg/kg every 2 weeks. PMID:28116649

Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas.

PubMed

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred W K; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-03-01

Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks.

Study of Variation in Dose Calculation Accuracy Between kV Cone-Beam Computed Tomography and kV fan-Beam Computed Tomography

PubMed Central

Kaliyaperumal, Venkatesan; Raphael, C. Jomon; Varghese, K. Mathew; Gopu, Paul; Sivakumar, S.; Boban, Minu; Raj, N. Arunai Nambi; Senthilnathan, K.; Babu, P. Ramesh

2017-01-01

Cone-beam computed tomography (CBCT) images are presently used for geometric verification for daily patient positioning. In this work, we have compared the images of CBCT with the images of conventional fan beam CT (FBCT) in terms of image quality and Hounsfield units (HUs). We also compared the dose calculated using CBCT with that of FBCT. Homogenous RW3 plates and Catphan phantom were scanned by FBCT and CBCT. In RW3 and Catphan phantom, percentage depth dose (PDD), profiles, isodose distributions (for intensity modulated radiotherapy plans), and calculated dose volume histograms were compared. The HU difference was within ± 20 HU (central region) and ± 30 HU (peripheral region) for homogeneous RW3 plates. In the Catphan phantom, the difference in HU was ± 20 HU in the central area and peripheral areas. The HU differences were within ± 30 HU for all HU ranges starting from −1000 to 990 in phantom and patient images. In treatment plans done with simple symmetric and asymmetric fields, dose difference (DD) between CBCT plan and FBCT plan was within 1.2% for both phantoms. In intensity modulated radiotherapy (IMRT) treatment plans, for different target volumes, the difference was <2%. This feasibility study investigated HU variation and dose calculation accuracy between FBCT and CBCT based planning and has validated inverse planning algorithms with CBCT. In our study, we observed a larger deviation of HU values in the peripheral region compared to the central region. This is due to the ring artifact and scatter contribution which may prevent the use of CBCT as the primary imaging modality for radiotherapy treatment planning. The reconstruction algorithm needs to be modified further for improving the image quality and accuracy in HU values. However, our study with TG-119 and intensity modulated radiotherapy test targets shows that CBCT can be used for adaptive replanning as the recalculation of dose with the anisotropic analytical algorithm is in full accord with conventional planning CT except in the build-up regions. Patient images with CBCT have to be carefully analyzed for any artifacts before using them for such dose calculations. PMID:28974864

A phase 1 trial of ABT-510 concurrent with standard chemoradiation for patients with newly diagnosed glioblastoma.

PubMed

Nabors, Louis B; Fiveash, John B; Markert, James M; Kekan, Manasi S; Gillespie, George Y; Huang, Zhi; Johnson, Martin J; Meleth, Sreelatha; Kuo, Huichien; Gladson, Candece L; Fathallah-Shaykh, Hassan M

2010-03-01

To determine the maximum tolerated dose of ABT-510, a thrombospondin-1 mimetic drug with antiangiogenic properties, when used concurrently with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma. Phase 1 dose-escalation clinical trial. Comprehensive Cancer Center, University of Alabama at Birmingham. Patients A total of 23 patients with newly diagnosed, histologically verified glioblastoma enrolled between April 2005 and January 2007. Four cohorts of 3 patients each received subcutaneous ABT-510 injection at doses of 20, 50, 100, or 200 mg/d. The maximum cohort was expanded to 14 patients to obtain additional safety and gene expression data. The treatment plan included 10 weeks of induction phase (temozolomide and radiotherapy with ABT-510 for 6 weeks plus ABT-510 monotherapy for 4 weeks) followed by a maintenance phase of ABT-510 and monthly temozolomide. Patients were monitored with brain magnetic resonance imaging and laboratory testing for dose-limiting toxicities, defined as grades 3 or 4 nonhematological toxicities and grade 4 hematological toxicities. Therapy was discontinued if 14 maintenance cycles were completed, disease progression occurred, or if the patient requested withdrawal. Disease progression, survival statistics, and gene expression arrays were analyzed. There were no grade 3 or 4 dose-limiting toxicity events that appeared related to ABT-510 for the dose range of 20 to 200 mg/d. A maximum tolerated dose was not defined. Most adverse events were mild, and injection-site reactions. The median time to tumor progression was 45.9 weeks, and the median overall survival time was 64.4 weeks. Gene expression analysis using TaqMan low-density arrays identified angiogenic genes that were differentially expressed in the brains of controls compared with patients with newly diagnosed glioblastoma, and identified FGF-1 and TIE-1 as being downregulated in patients who had better clinical outcomes. ABT-510, at subcutaneous doses up to 200 mg/d, is tolerated well with concurrent temozolomide and radiotherapy in patients with newly diagnosed glioblastoma, and low-density arrays provide a useful method of exploring gene expression profiles.

A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma.

PubMed

Martin, Thomas; Baz, Rachid; Benson, Don M; Lendvai, Nikoletta; Wolf, Jeffrey; Munster, Pamela; Lesokhin, Alexander M; Wack, Claudine; Charpentier, Eric; Campana, Frank; Vij, Ravi

2017-06-22

This phase 1b, open-label, dose-escalation study assessed the safety, efficacy, and pharmacokinetics of anti-CD38 monoclonal antibody isatuximab given in 2 schedules (3, 5, or 10 mg/kg every other week [Q2W] or 10 or 20 mg/kg weekly [QW] for 4 weeks and then Q2W thereafter [QW/Q2W]), in combination with lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (QW), in patients with relapsed/refractory multiple myeloma (RRMM). Patients received 28-day treatment cycles; the primary objective was to determine the maximum tolerated dose (MTD) of isatuximab with lenalidomide and dexamethasone. Fifty-seven patients (median 5 [range 1-12] prior regimens; 83% refractory to previous lenalidomide therapy) were treated. Median duration of dosing was 36.4 weeks; 15 patients remained on treatment at data cutoff. Isatuximab-lenalidomide-dexamethasone was generally well tolerated with only 1 dose-limiting toxicity reported (grade 3 pneumonia at 20 mg/kg QW/Q2W); the MTD was not reached. The most common isatuximab-related adverse events were infusion-associated reactions (IARs) (56%), which were grade 1/2 in 84% of patients who had an IAR and predominantly occurred during the first infusion. In the efficacy-evaluable population, the overall response rate (ORR) was 56% (29/52) and was similar between the 10 mg/kg Q2W and 10 and 20 mg/kg QW/Q2W cohorts. The ORR was 52% in 42 evaluable lenalidomide-refractory patients. Overall median progression-free survival was 8.5 months. Isatuximab exposure increased in a greater than dose-proportional manner; isatuximab and lenalidomide pharmacokinetic parameters appeared independent. These data suggest that isatuximab combined with lenalidomide and dexamethasone is active and tolerated in heavily pretreated patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT01749969. © 2017 by The American Society of Hematology.

A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis.

PubMed

Palmer, Melissa; Jennings, Lee; Silberg, Debra G; Bliss, Caleb; Martin, Patrick

2018-03-16

Accumulation of toxic free cholesterol in hepatocytes may cause hepatic inflammation and fibrosis. Volixibat inhibits bile acid reuptake via the apical sodium bile acid transporter located on the luminal surface of the ileum. The resulting increase in bile acid synthesis from cholesterol could be beneficial in patients with non-alcoholic steatohepatitis. This adaptive dose-finding study investigated the safety, tolerability, pharmacodynamics, and pharmacokinetics of volixibat. Overweight and obese adults were randomised 3:1 to double-blind volixibat or placebo, respectively, for 12 days. Volixibat was initiated at a once-daily dose of 20 mg, 40 mg or 80 mg. Based on the assessment of predefined safety events, volixibat dosing was either escalated or reduced. Other dose regimens (titrations and twice-daily dosing) were also evaluated. Assessments included safety, tolerability, stool hardness, faecal bile acid (FBA) excretion, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and lipids. All 84 randomised participants (volixibat, 63; placebo, 21) completed the study, with no serious adverse events at doses of up to 80 mg per day (maximum assessed dose). The median number of daily bowel evacuations increased from 1 (range 0-4) to 2 (0-8) during volixibat treatment, and stool was looser with volixibat than placebo. Volixibat was minimally absorbed; serum levels were rarely quantifiable at any dose or sampling time point, thereby precluding pharmacokinetic analyses. Mean daily FBA excretion was 930.61 μmol (standard deviation [SD] 468.965) with volixibat and 224.75 μmol (195.403) with placebo; effects were maximal at volixibat doses ≥20 mg/day. Mean serum C4 concentrations at day 12 were 98.767 ng/mL (standard deviation, 61.5841) with volixibat and 16.497 ng/mL (12.9150) with placebo. Total and low-density lipoprotein cholesterol levels decreased in the volixibat group, with median changes of - 0.70 mmol/L (range - 2.8 to 0.4) and - 0.6990 mmol/L (- 3.341 to 0.570), respectively. This study indicates that maximal inhibition of bile acid reabsorption, as assessed by FBA excretion, occurs at volixibat doses of ≥20 mg/day in obese and overweight adults, without appreciable change in gastrointestinal tolerability. These findings guided dose selection for an ongoing phase 2 study in patients with non-alcoholic steatohepatitis. ClinicalTrials.gov identifier: NCT02287779 (registration first received 6 November 2014).

Impact of Dietary Antioxidants on Sport Performance: A Review.

PubMed

Braakhuis, Andrea J; Hopkins, Will G

2015-07-01

Many athletes supplement with antioxidants in the belief this will reduce muscle damage, immune dysfunction and fatigue, and will thus improve performance, while some evidence suggests it impairs training adaptations. Here we review the effect of a range of dietary antioxidants and their effects on sport performance, including vitamin E, quercetin, resveratrol, beetroot juice, other food-derived polyphenols, spirulina and N-acetylcysteine (NAC). Older studies suggest vitamin E improves performance at altitude, with possible harmful effects on sea-level performance. Acute intake of vitamin E is worthy of further consideration, if plasma levels can be elevated sufficiently. Quercetin has a small beneficial effect for exercise of longer duration (>100 min), but it is unclear whether this benefits athletes. Resveratrol benefits trained rodents; more research is needed in athletes. Meta-analysis of beetroot juice studies has revealed that the nitrate component of beetroot juice had a substantial but unclear effect on performance when averaged across athletes, non-athletes and modes of exercise (single dose 1.4 ± 2.0%, double dose 0.5 ± 1.9%). The effect of addition of polyphenols and other components to beetroot juice was trivial but unclear (single dose 0.4 ± 3.2%, double dose -0.5 ± 3.3%). Other food-derived polyphenols indicate a range of performance outcomes from a large improvement to moderate impairment. Limited evidence suggests spirulina enhances endurance performance. Intravenous NAC improved endurance cycling performance and reduced muscle fatigue. On the basis of vitamin E and NAC studies, acute intake of antioxidants is likely to be beneficial. However, chronic intakes of most antioxidants have a harmful effect on performance.

Perioperative pharmacokinetics of methadone in adolescents.

PubMed

Sharma, Anshuman; Tallchief, Danielle; Blood, Jane; Kim, Thomas; London, Amy; Kharasch, Evan D

2011-12-01

Methadone is frequently administered to adults experiencing anesthesia and receiving pain treatment. Methadone pharmacokinetics in adults are well characterized, including the perioperative period. Methadone is also used in children. There is, however, no information on methadone pharmacokinetics in children of any age. The purpose of this investigation was to determine the pharmacokinetics of intravenous methadone in children undergoing surgery. Perioperative opioid-sparing effects were also assessed. Eligible subjects were children 5-18 yr undergoing general anesthesia and surgery, with an anticipated postoperative inpatient stay exceeding 3 days. Three groups of 10 to 11 patients each received intravenous methadone hydrochloride after anesthetic induction in ascending dose groups of 0.1, 0.2, and 0.3 mg/kg (up to 20 mg). Anesthetic care was not otherwise changed. Venous blood was obtained for 4 days, for stereoselective determination of methadone and metabolites. Pain assessments were made each morning. Daily and total opioid consumption was determined. Perioperative opioid consumption and pain was determined in a second cohort, which was matched to age, sex, race, ethnicity, surgical procedure, and length of stay, but not receiving methadone. The final methadone study cohort was 31 adolescents (14 ± 2 yr, range 10-18) undergoing major spine surgery for a diagnosis of scoliosis. Methadone pharmacokinetics were linear over the dose range 0.1-0.3 mg/kg. Disposition was stereoselective. Methadone administration did not dose-dependently affect postoperative pain scores, and did not dose-dependently decrease daily or total postoperative opioid consumption in spinal fusion patients. Methadone enantiomer disposition in adolescents undergoing surgery was similar to that in healthy adults.

Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis: A Dose-Ranging Study

PubMed Central

Chavoustie, Steven E.; Jacobs, Mark; Reisman, Howard A.; Waldbaum, Arthur S.; Levy, Sharon F.; Hillier, Sharon L.; Nyirjesy, Paul

2015-01-01

Objective Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration–approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. Materials and Methods This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. Results In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Conclusions Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days. PMID:24983350

Metronidazole vaginal gel 1.3% in the treatment of bacterial vaginosis: a dose-ranging study.

PubMed

Chavoustie, Steven E; Jacobs, Mark; Reisman, Howard A; Waldbaum, Arthur S; Levy, Sharon F; Hillier, Sharon L; Nyirjesy, Paul

2015-04-01

Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration-approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days.

A phase I and pharmacokinetic study of a powder-filled capsule formulation of oral irinotecan (CPT-11) given daily for 5 days every 3 weeks in patients with advanced solid tumors.

PubMed

Pitot, Henry C; Adjei, Alex A; Reid, Joel M; Sloan, Jeff A; Atherton, Pamela J; Rubin, Joseph; Alberts, Steven R; Duncan, Barbara A; Denis, Louis; Schaaf, Larry J; Yin, Donghua; Sharma, Amarnath; McGovren, Patrick; Miller, Langdon L; Erlichman, Charles

2006-08-01

Intravenous (i.v.) irinotecan is a cytotoxic topoisomerase I inhibitor with broad clinical activity in metastatic colorectal cancer and other tumors. The development of an oral formulation of irinotecan could enhance convenience and lessen the expense of palliative irinotecan delivery. This phase I study evaluated the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of irinotecan given as a powder-filled capsule (PFC) daily for 5 days every 3 weeks. Patients with advanced solid tumors received escalating doses of oral irinotecan daily for 5 days every 3 weeks. Plasma samples were collected following the first and fifth doses of irinotecan during Cycle 1 to determine the PK of irinotecan and its major circulating metabolites: SN-38, SN-38G, and APC. 20 patients (median age 61.5 years, range 40-75; M/F 12/8; ECOG PS 0=5, 1=11, 2=4) received oral irinotecan at dose levels of 30 (n=3), 40 (n=3), 50 (n=6), and 60 (n=8) mg/m(2)/day. Of the eight patients enrolled at 60 mg/m(2), three patients experienced DLT (> or = grade 3) consisting of nausea (three patients), vomiting (three patients), diarrhea (two patients), and febrile neutropenia (two patients) for which all the three patients required hospitalization. Treatment of six patients at the 50-mg/m(2) dose level resulted in no DLT. Other toxicities observed include abdominal pain, alopecia, anorexia, and asthenia. After oral administration, irinotecan was rapidly absorbed into systemic circulation and converted to the active metabolite SN-38. Increasing dose levels resulted in a dose-dependent increase in mean exposure parameters (Cmax and AUC) of irinotecan and metabolites. Systemic exposure parameters (Cmax and AUC(0-24)) of irinotecan and SN-38 were comparable between days 1 and 5. The extent of conversion from irinotecan to SN-38 was approximately threefold higher after the oral administration compared to that previously observed after i.v. administration. The exposure parameters of irinotecan or SN-38 are of limited value in predicting severity of Cycle 1 toxicities in the twofold dose range evaluated. Daily oral administration of irinotecan as the PFC formulation for 5 days every 3 weeks can safely deliver protracted exposure to SN-38, with the MTD of 50 mg/m(2)/d.

Variation in absorption and half-life of hydrocortisone influence plasma cortisol concentrations.

PubMed

Hindmarsh, Peter C; Charmandari, Evangelia

2015-04-01

Hydrocortisone therapy should be individualized in congenital adrenal hyperplasia (CAH) patients to avoid over and under replacement. We have assessed how differences in absorption and half-life of cortisol influence glucocorticoid exposure. Forty-eight patients (21 M) aged between 6·1 and 20·3 years with CAH due to CYP21A2 deficiency were studied. Each patient underwent a 24-h plasma cortisol profile with the morning dose used to calculate absorption parameters along with an intravenous (IV) hydrocortisone (15 mg/m(2) body surface area) bolus assessment of half-life. Parameters derived were maximum plasma concentration (Cmax ), time of maximum plasma concentration (tmax ), time to attaining plasma cortisol concentration <100 nmol/l and half-life of cortisol. Mean half-life was 76·5 ± 5·2 (range 40-225·3) min, Cmax 780·7 ± 61·6 nmol/l and tmax 66·7 (range 20-118) min. Time taken to a plasma cortisol concentration less than 100 nmol/l was 289 (range 140-540) min. Those with a fast half-life and slow tmax took longest to reach a plasma cortisol concentration less than 100 nmol/l (380 ± 34·6 min), compared to those with a slow half-life and fast tmax (298 ± 34·8 min) and those with a fast half-life and fast tmax (249·5 ± 14·4 min) (One-way anovaF = 4·52; P = 0·009). Both rate of absorption and half-life of cortisol in the circulation play important roles in determining overall exposure to oral glucocorticoid. Dose regimens need to incorporate estimates of these parameters into determining the optimum dosing schedule for individuals. © 2014 John Wiley & Sons Ltd.

Cardiac valve calcifications on low-dose unenhanced ungated chest computed tomography: inter-observer and inter-examination reliability, agreement and variability.

PubMed

van Hamersvelt, Robbert W; Willemink, Martin J; Takx, Richard A P; Eikendal, Anouk L M; Budde, Ricardo P J; Leiner, Tim; Mol, Christian P; Isgum, Ivana; de Jong, Pim A

2014-07-01

To determine inter-observer and inter-examination variability for aortic valve calcification (AVC) and mitral valve and annulus calcification (MC) in low-dose unenhanced ungated lung cancer screening chest computed tomography (CT). We included 578 lung cancer screening trial participants who were examined by CT twice within 3 months to follow indeterminate pulmonary nodules. On these CTs, AVC and MC were measured in cubic millimetres. One hundred CTs were examined by five observers to determine the inter-observer variability. Reliability was assessed by kappa statistics (κ) and intra-class correlation coefficients (ICCs). Variability was expressed as the mean difference ± standard deviation (SD). Inter-examination reliability was excellent for AVC (κ = 0.94, ICC = 0.96) and MC (κ = 0.95, ICC = 0.90). Inter-examination variability was 12.7 ± 118.2 mm(3) for AVC and 31.5 ± 219.2 mm(3) for MC. Inter-observer reliability ranged from κ = 0.68 to κ = 0.92 for AVC and from κ = 0.20 to κ = 0.66 for MC. Inter-observer ICC was 0.94 for AVC and ranged from 0.56 to 0.97 for MC. Inter-observer variability ranged from -30.5 ± 252.0 mm(3) to 84.0 ± 240.5 mm(3) for AVC and from -95.2 ± 210.0 mm(3) to 303.7 ± 501.6 mm(3) for MC. AVC can be quantified with excellent reliability on ungated unenhanced low-dose chest CT, but manual detection of MC can be subject to substantial inter-observer variability. Lung cancer screening CT may be used for detection and quantification of cardiac valve calcifications. • Low-dose unenhanced ungated chest computed tomography can detect cardiac valve calcifications. • However, calcified cardiac valves are not reported by most radiologists. • Inter-observer and inter-examination variability of aortic valve calcifications is sufficient for longitudinal studies. • Volumetric measurement variability of mitral valve and annulus calcifications is substantial.

Effects of single doses of rabeprazole 20 mg and esomeprazole 40 mg on 24-h intragastric pH in healthy subjects.

PubMed

Warrington, Steve; Baisley, Kathy; Dunn, Kate; Boyce, Malcolm; Morocutti, Anna

2006-09-01

To compare antisecretory effects of single doses of rabeprazole and esomeprazole. Open, randomised, 2-way crossover, clinical pharmacology study. 24 healthy subjects (10 men; mean age 26.2 y) received a single dose of rabeprazole 20 mg or esomeprazole 40 mg, with a 14-day 'washout'. Intragastric pH was recorded continuously from 24 h before to 24 h after dosing. Mean intragastric pH was higher after esomeprazole than rabeprazole during 0-5 h after dosing (P=0.0001); the reverse was true from 14-24 h (P=0.0002). Mean % time pH>3 and >4 was greater after esomeprazole than rabeprazole during 0-14 h (P=0.041 and 0.044), but the reverse was true during 14-24 h (P=0.0005 and 0.001). In the 0-24 h interval as a whole, there was no difference between treatments in mean pH or % time pH>3 or >4. Single-dose rabeprazole 20 mg was as effective as esomeprazole 40 mg in increasing intragastric pH and maintaining pH>3 and >4, despite the 2-fold difference in dose.

New Fetal Dose Estimates from 18F-FDG Administered During Pregnancy: Standardization of Dose Calculations and Estimations with Voxel-Based Anthropomorphic Phantoms.

PubMed

Zanotti-Fregonara, Paolo; Chastan, Mathieu; Edet-Sanson, Agathe; Ekmekcioglu, Ozgul; Erdogan, Ezgi Basak; Hapdey, Sebastien; Hindie, Elif; Stabin, Michael G

2016-11-01

Data from the literature show that the fetal absorbed dose from 18 F-FDG administration to the pregnant mother ranges from 0.5E-2 to 4E-2 mGy/MBq. These figures were, however, obtained using different quantification techniques and with basic geometric anthropomorphic phantoms. The aim of this study was to refine the fetal dose estimates of published as well as new cases using realistic voxel-based phantoms. The 18 F-FDG doses to the fetus (n = 19; 5-34 wk of pregnancy) were calculated with new voxel-based anthropomorphic phantoms of the pregnant woman. The image-derived fetal time-integrated activity values were combined with those of the mothers' organs from the International Commission on Radiological Protection publication 106 and the dynamic bladder model with a 1-h bladder-voiding interval. The dose to the uterus was used as a proxy for early pregnancy (up to 10 wk). The time-integrated activities were entered into OLINDA/EXM 1.1 to derive the dose with the classic anthropomorphic phantoms of pregnant women, then into OLINDA/EXM 2.0 to assess the dose using new voxel-based phantoms. The average fetal doses (mGy/MBq) with OLINDA/EXM 2.0 were 2.5E-02 in early pregnancy, 1.3E-02 in the late part of the first trimester, 8.5E-03 in the second trimester, and 5.1E-03 in the third trimester. The differences compared with the doses calculated with OLINDA/EXM 1.1 were +7%, +70%, +35%, and -8%, respectively. Except in late pregnancy, the doses estimated with realistic voxelwise anthropomorphic phantoms are higher than the doses derived from old geometric phantoms. The doses remain, however, well below the threshold for any deterministic effects. Thus, pregnancy is not an absolute contraindication of a clinically justified 18 F-FDG PET scan. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Committed effective dose from naturally occuring radionuclides in shellfish

NASA Astrophysics Data System (ADS)

Khandaker, Mayeen Uddin; Wahib, Norfadira Binti; Amin, Yusoff Mohd.; Bradley, D. A.

2013-07-01

Recognizing their importance in the average Malaysian daily diet, the radioactivity concentrations in mollusc- and crustacean-based food have been determined for key naturally occuring radionuclides. Fresh samples collected from various maritime locations around peninsular Malaysia have been processed using standard procedures; the radionuclide concentrations being determined using an HPGe γ-ray spectrometer. For molluscs, assuming secular equilibrium, the range of activities of 238U (226Ra), 232Th (228Ra) and 40K were found to be 3.28±0.35 to 5.34±0.52, 1.20±0.21 to 2.44±0.21 and 118±6 to 281±14 Bq kg-1 dry weight, respectively. The respective values for crustaceans were 3.02±0.57 to 4.70±0.52, 1.38±0.21 to 2.40±0.35 and 216±11 to 316±15 Bq kg-1. The estimated average daily intake of radioactivity from consumption of molluscs are 0.37 Bq kg-1 for 238U (226Ra), 0.16 Bq kg-1 for 232Th (228Ra) and 18 Bq kg-1 for 40K; the respective daily intake values from crustaceans are 0.36 Bq kg-1, 0.16 Bq kg-1 and 23 Bq kg-1. Associated annual committed effective doses from molluscs are estimated to be in the range 21.3 to 34.7 μSv for 226Ra, 19.3 to 39.1 μSv for 228Ra and 17.0 to 40.4 μSv for 40K. For crustaceans, the respective dose ranges are 19.6 to 30.5 μSv, 22.0 to 38.4 μSv and 31.1 to 45.5 μSv, being some several times world average values.

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study

PubMed Central

Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)–4.29 mSv), 0.37 mSv (range: ND–3.61 mSv), 0.22 mSv (range: ND–1.44 mSv), 0.20 mSv (range: ND–1.87 mSv), and 0.17 mSv (range: ND–0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04–0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses. PMID:28235009

Survival of Salmonella typhimurium ATCC 14028 on the surface of chicken legs or in mechanically deboned chicken meat gamma irradiated in air or vacuum at temperatures of -20 to +20 C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thayer, D.W.; Boyd, G.

1991-04-01

Response-surface methodology was used to develop predictive equations for the response of Salmonella typhimurium ATCC 14028 on the surface of chicken legs or within mechanically deboned chicken meat (MDCM) to the effects of {gamma} radiation doses of 0 to 3.60 kGy (100 krad = 1 kGy) at temperatures of -20 to +20 C in air or vacuum. A streptomycin-resistant mutant was used in these studies to allow accurate estimations of the surviving salmonellae in the presence of residual normal flora. This strain has been demonstrated to have no significant shift in its biological properties nor in its resistance to ionizingmore » radiation. The response of S. typhimurium to gamma radiation was similar on both chicken legs and MDCM. The radiation was significantly more lethal to the bacterial cells at temperatures above freezing. The response-surface equations developed from the studies predict that the number of viable cells per gram of MDCM or per square centimeter of the surface of chicken legs would be reduced approximately 2.8 to 5.1 log units at 0 C by radiation doses within the range of 1.5 to 3.0 kGy. The results of the present studies are similar to those obtained previously with sterile mechanically deboned chicken meat.« less

Monte Carlo simulation of TrueBeam flattening-filter-free beams using Varian phase-space files: Comparison with experimental data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belosi, Maria F.; Fogliata, Antonella, E-mail: antonella.fogliata-cozzi@eoc.ch, E-mail: afc@iosi.ch; Cozzi, Luca

2014-05-15

Purpose: Phase-space files for Monte Carlo simulation of the Varian TrueBeam beams have been made available by Varian. The aim of this study is to evaluate the accuracy of the distributed phase-space files for flattening filter free (FFF) beams, against experimental measurements from ten TrueBeam Linacs. Methods: The phase-space files have been used as input in PRIMO, a recently released Monte Carlo program based on thePENELOPE code. Simulations of 6 and 10 MV FFF were computed in a virtual water phantom for field sizes 3 × 3, 6 × 6, and 10 × 10 cm{sup 2} using 1 × 1more » × 1 mm{sup 3} voxels and for 20 × 20 and 40 × 40 cm{sup 2} with 2 × 2 × 2 mm{sup 3} voxels. The particles contained in the initial phase-space files were transported downstream to a plane just above the phantom surface, where a subsequent phase-space file was tallied. Particles were transported downstream this second phase-space file to the water phantom. Experimental data consisted of depth doses and profiles at five different depths acquired at SSD = 100 cm (seven datasets) and SSD = 90 cm (three datasets). Simulations and experimental data were compared in terms of dose difference. Gamma analysis was also performed using 1%, 1 mm and 2%, 2 mm criteria of dose-difference and distance-to-agreement, respectively. Additionally, the parameters characterizing the dose profiles of unflattened beams were evaluated for both measurements and simulations. Results: Analysis of depth dose curves showed that dose differences increased with increasing field size and depth; this effect might be partly motivated due to an underestimation of the primary beam energy used to compute the phase-space files. Average dose differences reached 1% for the largest field size. Lateral profiles presented dose differences well within 1% for fields up to 20 × 20 cm{sup 2}, while the discrepancy increased toward 2% in the 40 × 40 cm{sup 2} cases. Gamma analysis resulted in an agreement of 100% when a 2%, 2 mm criterion was used, with the only exception of the 40 × 40 cm{sup 2} field (∼95% agreement). With the more stringent criteria of 1%, 1 mm, the agreement reduced to almost 95% for field sizes up to 10 × 10 cm{sup 2}, worse for larger fields. Unflatness and slope FFF-specific parameters are in line with the possible energy underestimation of the simulated results relative to experimental data. Conclusions: The agreement between Monte Carlo simulations and experimental data proved that the evaluated Varian phase-space files for FFF beams from TrueBeam can be used as radiation sources for accurate Monte Carlo dose estimation, especially for field sizes up to 10 × 10 cm{sup 2}, that is the range of field sizes mostly used in combination to the FFF, high dose rate beams.« less

[Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

PubMed

Sokić, D; Janković, S M

1994-01-01

Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

Digital radiography: optimization of image quality and dose using multi-frequency software.

PubMed

Precht, H; Gerke, O; Rosendahl, K; Tingberg, A; Waaler, D

2012-09-01

New developments in processing of digital radiographs (DR), including multi-frequency processing (MFP), allow optimization of image quality and radiation dose. This is particularly promising in children as they are believed to be more sensitive to ionizing radiation than adults. To examine whether the use of MFP software reduces the radiation dose without compromising quality at DR of the femur in 5-year-old-equivalent anthropomorphic and technical phantoms. A total of 110 images of an anthropomorphic phantom were imaged on a DR system (Canon DR with CXDI-50 C detector and MLT[S] software) and analyzed by three pediatric radiologists using Visual Grading Analysis. In addition, 3,500 images taken of a technical contrast-detail phantom (CDRAD 2.0) provide an objective image-quality assessment. Optimal image-quality was maintained at a dose reduction of 61% with MLT(S) optimized images. Even for images of diagnostic quality, MLT(S) provided a dose reduction of 88% as compared to the reference image. Software impact on image quality was found significant for dose (mAs), dynamic range dark region and frequency band. By optimizing image processing parameters, a significant dose reduction is possible without significant loss of image quality.

Volumetric-modulated arc therapy for the treatment of a large planning target volume in thoracic esophageal cancer.

PubMed

Abbas, Ahmar S; Moseley, Douglas; Kassam, Zahra; Kim, Sun Mo; Cho, Charles

2013-05-06

Recently, volumetric-modulated arc therapy (VMAT) has demonstrated the ability to deliver radiation dose precisely and accurately with a shorter delivery time compared to conventional intensity-modulated fixed-field treatment (IMRT). We applied the hypothesis of VMAT technique for the treatment of thoracic esophageal carcinoma to determine superior or equivalent conformal dose coverage for a large thoracic esophageal planning target volume (PTV) with superior or equivalent sparing of organs-at-risk (OARs) doses, and reduce delivery time and monitor units (MUs), in comparison with conventional fixed-field IMRT plans. We also analyzed and compared some other important metrics of treatment planning and treatment delivery for both IMRT and VMAT techniques. These metrics include: 1) the integral dose and the volume receiving intermediate dose levels between IMRT and VMATI plans; 2) the use of 4D CT to determine the internal motion margin; and 3) evaluating the dosimetry of every plan through patient-specific QA. These factors may impact the overall treatment plan quality and outcomes from the individual planning technique used. In this study, we also examined the significance of using two arcs vs. a single-arc VMAT technique for PTV coverage, OARs doses, monitor units and delivery time. Thirteen patients, stage T2-T3 N0-N1 (TNM AJCC 7th edn.), PTV volume median 395 cc (range 281-601 cc), median age 69 years (range 53 to 85), were treated from July 2010 to June 2011 with a four-field (n = 4) or five-field (n = 9) step-and-shoot IMRT technique using a 6 MV beam to a prescribed dose of 50 Gy in 20 to 25 F. These patients were retrospectively replanned using single arc (VMATI, 91 control points) and two arcs (VMATII, 182 control points). All treatment plans of the 13 study cases were evaluated using various dose-volume metrics. These included PTV D99, PTV D95, PTV V9547.5Gy(95%), PTV mean dose, Dmax, PTV dose conformity (Van't Riet conformation number (CN)), mean lung dose, lung V20 and V5, liver V30, and Dmax to the spinal canal prv3mm. Also examined were the total plan monitor units (MUs) and the beam delivery time. Equivalent target coverage was observed with both VMAT single and two-arc plans. The comparison of VMATI with fixed-field IMRT demonstrated equivalent target coverage; statistically no significant difference were found in PTV D99 (p = 0.47), PTV mean (p = 0.12), PTV D95 and PTV V9547.5Gy (95%) (p = 0.38). However, Dmax in VMATI plans was significantly lower compared to IMRT (p = 0.02). The Van't Riet dose conformation number (CN) was also statistically in favor of VMATI plans (p = 0.04). VMATI achieved lower lung V20 (p = 0.05), whereas lung V5 (p = 0.35) and mean lung dose (p = 0.62) were not significantly different. The other OARs, including spinal canal, liver, heart, and kidneys showed no statistically significant differences between the two techniques. Treatment time delivery for VMATI plans was reduced by up to 55% (p = 5.8E-10) and MUs reduced by up to 16% (p = 0.001). Integral dose was not statistically different between the two planning techniques (p = 0.99). There were no statistically significant differences found in dose distribution of the two VMAT techniques (VMATI vs. VMATII) Dose statistics for both VMAT techniques were: PTV D99 (p = 0.76), PTV D95 (p = 0.95), mean PTV dose (p = 0.78), conformation number (CN) (p = 0.26), and MUs (p = 0.1). However, the treatment delivery time for VMATII increased significantly by two-fold (p = 3.0E-11) compared to VMATI. VMAT-based treatment planning is safe and deliverable for patients with thoracic esophageal cancer with similar planning goals, when compared to standard IMRT. The key benefit for VMATI was the reduction in treatment delivery time and MUs, and improvement in dose conformality. In our study, we found no significant difference in VMATII over single-arc VMATI for PTV coverage or OARs doses. However, we observed significant increase in delivery time for VMATII compared to VMATI.

Dose enhancement in radiotherapy of small lung tumors using inline magnetic fields: A Monte Carlo based planning study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oborn, B. M., E-mail: brad.oborn@gmail.com; Ge, Y.; Hardcastle, N.

2016-01-15

Purpose: To report on significant dose enhancement effects caused by magnetic fields aligned parallel to 6 MV photon beam radiotherapy of small lung tumors. Findings are applicable to future inline MRI-guided radiotherapy systems. Methods: A total of eight clinical lung tumor cases were recalculated using Monte Carlo methods, and external magnetic fields of 0.5, 1.0, and 3 T were included to observe the impact on dose to the planning target volume (PTV) and gross tumor volume (GTV). Three plans were 6 MV 3D-CRT plans while 6 were 6 MV IMRT. The GTV’s ranged from 0.8 to 16 cm{sup 3}, whilemore » the PTV’s ranged from 1 to 59 cm{sup 3}. In addition, the dose changes in a 30 cm diameter cylindrical water phantom were investigated for small beams. The central 20 cm of this phantom contained either water or lung density insert. Results: For single beams, an inline magnetic field of 1 T has a small impact in lung dose distributions by reducing the lateral scatter of secondary electrons, resulting in a small dose increase along the beam. Superposition of multiple small beams leads to significant dose enhancements. Clinically, this process occurs in the lung tissue typically surrounding the GTV, resulting in increases to the D{sub 98%} (PTV). Two isolated tumors with very small PTVs (3 and 6 cm{sup 3}) showed increases in D{sub 98%} of 23% and 22%. Larger PTVs of 13, 26, and 59 cm{sup 3} had increases of 9%, 6%, and 4%, describing a natural fall-off in enhancement with increasing PTV size. However, three PTVs bounded to the lung wall showed no significant increase, due to lack of dose enhancement in the denser PTV volume. In general, at 0.5 T, the GTV mean dose enhancement is around 60% lower than that at 1 T, while at 3 T, it is 5%–60% higher than 1 T. Conclusions: Monte Carlo methods have described significant and predictable dose enhancement effects in small lung tumor plans for 6 MV radiotherapy when an external inline magnetic field is included. Results of this study indicate that future clinical inline MRI-guided radiotherapy systems will be able to deliver a dosimetrically superior treatment to small (PTV < 15 cm{sup 3}), isolated lung tumors over non-MRI-Linac systems. This increased efficacy coincides with the reimbursement in the United States of lung CT screening and the likely rapid growth in the number of patients with small lung tumors to be treated with radiotherapy.« less

Phosphine Resistance in Adult and Immature Life Stages of Tribolium castaneum (Coleoptera: Tenebrionidae) and Plodia interpunctella (Lepidoptera: Pyralidae) Populations in California.

PubMed

Gautam, S G; Opit, G P; Hosoda, E

2016-12-01

Phosphine resistance in stored-product insects occurs worldwide and is a major challenge to continued effective use of this fumigant. We determined resistance frequencies and levels of resistance in Tribolium castaneum and Plodia interpunctella collected from California almond storage and processing facilities. Discriminating doses of phosphine were established for eggs and larvae of P. interpunctella and eggs of T. castaneum using laboratory susceptible strains of the two species. For T. castaneum and P. interpunctella eggs, discriminating doses were 62.4 and 107.8 ppm, respectively, over a 3-d fumigation period, and for P. interpunctella larvae, discriminating dose was 98.7 ppm over a 20-h fumigation period. Discriminating dose tests on adults and eggs showed that 4 out of 11 T. castaneum populations tested had resistance frequencies that ranged from 42 to 100% for adults and 54 to 100% for eggs. LC99 values for the susceptible and the most resistant adults of T. castaneum were 7.4 and 356.9 ppm over 3 d, respectively. LC99 values for T. castaneum eggs were 51.5 and 653.9 ppm, respectively. Based on adult data, the most resistant T. castaneum beetle population was 49× more resistant than the susceptible strain. Phosphine resistance frequencies in P. interpunctella eggs ranged from 4 to 20%. Results show phosphine resistance is present in both species in California. Future research will investigate phosphine resistance over a wider geographic area. In addition, the history of pest management practices in facilities where insects tested in this study originated will be determined in order to develop phosphine resistance management strategies for California almond storage and processing facilities. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ierardi, Anna Maria; Duka, Ejona; Radaelli, Alessandro

AimTo evaluate the feasibility of image fusion (IF) of pre-procedural arterial-phase CT angiography or MR angiography with intra-procedural fluoroscopy for road-mapping in endovascular treatment of aorto-iliac steno-occlusive disease.Materials and MethodsBetween September and November, 2014, we prospectively evaluated 5 patients with chronic aorto-iliac steno-occlusive disease, who underwent endovascular treatment in the angiography suite. Fusion image road-mapping was performed using angiographic phase CT images or MR images acquired before and intra-procedural unenhanced cone-beam CT. Radiation dose of the procedure, volume of intra-procedural iodinated contrast medium, fluoroscopy time, and overall procedural time were recorded. Reasons for potential fusion imaging inaccuracies were also evaluated.ResultsImagemore » co-registration and fusion guidance were feasible in all procedures. Mean radiation dose of the procedure was 60.21 Gycm2 (range 55.02–63.75 Gycm2). The mean total procedure time was 32.2 min (range 27–38 min). The mean fluoroscopy time was 12 min and 3 s. The mean procedural iodinated contrast material dose was 24 mL (range 20–40 mL).ConclusionsIF gives Interventional Radiologists the opportunity to use new technologies in order to improve outcomes with a significant reduction of contrast media administration.« less

SU-E-T-289: Dose-Volume-Effect Relationships for Lung Cancer Patients Treated with SBRT On a Prospective Protocol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayyas, E; Brown, S; Liu, J

Purpose: Stereotactic body radiotherapy (SBRT) is commonly used to treat early stage lung tumors. This study was designed to evaluate associations between dose, volume and clinical outcomes including analysis of both clinical toxicity scores and quality of life (QOL) data for non-small cell lung cancer patients treated with SBRT. Preliminary results are presented. Methods: Sixty-seven NSCLC patients, 46 primarily with early stage, and 21 with recurrent disease were treated with dose regimens consisting mainly of 12 Gy x 4 fractions, and 3 or 5 fractions at lower dose, for patients with recurrent disease (Table 1). Follow-up data is being collectedmore » at baseline, after treatment and at 3, 6, 12, 18 and 24 months post-treatment. Clinical follow-up data acquired to date was assessed using the Charlson Comorbidity Clinical and Toxicity Scoring forms. QOL data was evaluated using the EQ-5D, and FACT-TOI validated surveys. All outcomes surveys are collected within an “in-house” developed outcomes database. Results: The median follow-up was 3.5±0.8 months. Mean lung doses (MLD) were converted to BED-2 Gy using the linear-quadratic model with an alpha/beta=3.0. Average MLD was 3.7+3.1 Gy (range: 0.4–20.9 Gy). The percentages of patients with > grade 2 cough, dyspnea and fatigue were 13.3, 17.0, 6.3%, respectively. Preliminary analyses (at 3 months after SBRT) show a mild correlation between MLD > 2 Gy and > grade 2 cough (borderline significant) and dyspnea (significant, p<0.05). One patient was observed with a grade 3 cough. Given the short follow-up, tumor control is not yet assessable. Conclusion: The SBRT dose fractionation regimen of 12 Gy x 4 was well tolerated at early time points. Additional follow-up is required to assess the long-term clinical outcome efficacy and toxicity profiles of the dose regimen.« less

SU-F-T-184: 3D Range-Modulator for Scanned Particle Therapy: Development, Monte Carlo Simulations and Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simeonov, Y; Penchev, P; Ringbaek, T Printz

2016-06-15

Purpose: Active raster scanning in particle therapy results in highly conformal dose distributions. Treatment time, however, is relatively high due to the large number of different iso-energy layers used. By using only one energy and the so called 3D range-modulator irradiation times of a few seconds only can be achieved, thus making delivery of homogeneous dose to moving targets (e.g. lung cancer) more reliable. Methods: A 3D range-modulator consisting of many pins with base area of 2.25 mm2 and different lengths was developed and manufactured with rapid prototyping technique. The form of the 3D range-modulator was optimised for a sphericalmore » target volume with 5 cm diameter placed at 25 cm in a water phantom. Monte Carlo simulations using the FLUKA package were carried out to evaluate the modulating effect of the 3D range-modulator and simulate the resulting dose distribution. The fine and complicated contour form of the 3D range-modulator was taken into account by a specially programmed user routine. Additionally FLUKA was extended with the capability of intensity modulated scanning. To verify the simulation results dose measurements were carried out at the Heidelberg Ion Therapy Center (HIT) with a 400.41 MeV 12C beam. Results: The high resolution measurements show that the 3D range-modulator is capable of producing homogeneous 3D conformal dose distributions, simultaneously reducing significantly irradiation time. Measured dose is in very good agreement with the previously conducted FLUKA simulations, where slight differences were traced back to minor manufacturing deviations from the perfect optimised form. Conclusion: Combined with the advantages of very short treatment time the 3D range-modulator could be an alternative to treat small to medium sized tumours (e.g. lung metastasis) with the same conformity as full raster-scanning treatment. Further simulations and measurements of more complex cases will be conducted to investigate the full potential of the 3D range-modulator.« less

Use of fluorine-18-BPA PET images and image registration to enhance radiation treatment planning for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Khan, Mohammad Khurram

The Monte-Carlo based simulation environment for radiation therapy (SERA) software is used to simulate the dose administered to a patient undergoing boron neutron capture therapy (BNCT). Point sampling of tumor tissue results in an estimate of a uniform boron concentration scaling factor of 3.5. Under conventional treatment protocols, this factor is used to scale the boron component of the dose linearly and homogenously within the tumor and target volumes. The average dose to the tumor cells by such a method could be improved by better methods of quantifying the in-vivo 10B biodistribution. A better method includes radiolabeling para-Boronophenylalanine (p-BPA) with 18F and imaging the pharmaceutical using positron emission tomography (PET). This biodistribution of 18F-BPA can then be used to better predict the average dose delivered to the tumor regions. This work uses registered 18F-BPA PET images to incorporate the in-vivo boron biodistribution within current treatment planning. The registered 18F-BPA PET images are then coupled in a new computer software, PET2MRI.m, to linearly scale the boron component of the dose. A qualititative and quantitative assessment of the dose contours is presented using the two approaches. Tumor volume, tumor axial extent, and target locations are compared between using MRI or PET images to define the tumor volume. In addition, peak-to-normal brain value at tumor axial center is determined for pre and post surgery patients using 18F-BPA PET images. The differences noted between the registered GBM tumor volumes (range: 34.04--136.36%), tumor axial extent (range: 20--150%), and the beam target location (1.27--4.29 cm) are significantly different. The peak-to-normal brain values are also determined at the tumor axial center using the 18F-BPA PET images. The peak-to-normal brain values using the last frame of the pre-surgery study for the GBM patients ranged from 2.05--3.4. For post surgery time weighted PET data, the peak-to-normal brain value in the residual parts of the tumor ranged from 1.5--1.7. Qualitatively, boron dose contours are greatly shifted using PET images when compared with MRI images. Collectively, these differences can lead to significant reorientation of the beam and can significantly impact current BNCT treatment planning.

A prospective study on radiation-induced changes in hearing function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrmann, Franziska; Doerr, Wolfgang; Experimental Center, Medical Faculty Carl Gustav Carus, University of Technology-Dresden, Dresden

Purpose: To quantitate changes in hearing function after radiotherapy for head-and-neck tumors. Methods and Materials: At the Department of Radiotherapy and Radiation Oncology, 32 patients were irradiated for head-and-neck tumors. Three-dimensional treatment planning was applied. Total tumor doses were 30.0-77.6 Gy, local doses to the inner ear (n = 64) ranged from 1.7 to 64.3 Gy. Audiometry was performed before the onset of radiotherapy (RT), at a tumor dose of 40 Gy or at the end of palliative treatment, at the end of curative RT, and 2-6 months post-RT. Assays applied were frequency-specific threshold measurements for air and bone conduction,more » measurements according to Weber and Rinne, tympanometry and assessment of the stapedius reflex. Results: Age and prior disease significantly decreased, whereas previous or concurrent alcohol consumption significantly increased hearing ability. A significant reduction in hearing ability during RT was found for high frequencies (at 40 Gy) and low frequencies (at end of RT), which persisted after RT. No differences were observed for air or bone conduction. None of the other assays displayed time- or dose-dependent changes. Dose-effect analyses revealed an ED50 (dose at which a 50% incidence is expected) for significant changes in hearing thresholds (15 dB) in the range of 20-25 Gy, with large confidence limits. Conclusions: Radiation effects on hearing ability were confined to threshold audiogram values, which started during the treatment without reversibility during 6 months postradiotherapy.« less

Retrospective review of Contura HDR breast cases to improve our standardized procedure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iftimia, Ileana, E-mail: Ileana.n.iftimia@lahey.org; Cirino, Eileen T.; Ladd, Ron

2013-07-01

To retrospectively review our first 20 Contura high dose rate breast cases to improve and refine our standardized procedure and checklists. We prepared in advance checklists for all steps, developed an in-house Excel spreadsheet for second checking the plan, and generated a procedure for efficient contouring and a set of optimization constraints to meet the dose volume histogram criteria. Templates were created in our treatment planning system for structures, isodose levels, optimization constraints, and plan report. This study reviews our first 20 high dose rate Contura breast treatment plans. We followed our standardized procedure for contouring, planning, and second checking.more » The established dose volume histogram criteria were successfully met for all plans. For the cases studied here, the balloon-skin and balloon-ribs distances ranged between 5 and 43 mm and 1 and 33 mm, respectively; air{sub s}eroma volume/PTV{sub E}val volume≤5.5% (allowed≤10%); asymmetry<1.2 mm (goal≤2 mm); PTV{sub E}val V90%≥97.6%; PTV{sub E}val V95%≥94.9%; skin max dose≤98%Rx; ribs max dose≤137%Rx; V150%≤29.8 cc; V200%≤7.8 cc; the total dwell time range was 225.4 to 401.9 seconds; and the second check agreement was within 3%. Based on this analysis, more appropriate ranges for the total dwell time and balloon diameter tolerance were found. Three major problems were encountered: balloon migration toward the skin for small balloon-to-skin distances, lumen obstruction, and length change for the flexible balloon. Solutions were found for these issues and our standardized procedure and checklists were updated accordingly. Based on our review of these cases, the use of checklists resulted in consistent results, indicating good coverage for the target without sacrificing the critical structures. This review helped us to refine our standardized procedure and update our checklists.« less

Estimating thyroid dose in pediatric CT exams from surface dose measurement

NASA Astrophysics Data System (ADS)

Al-Senan, Rani; Mueller, Deborah L.; Hatab, Mustapha R.

2012-07-01

The purpose of this study was to investigate the possibility of estimating pediatric thyroid doses from CT using surface neck doses. Optically stimulated luminescence dosimeters were used to measure the neck surface dose of 25 children ranging in ages between one and three years old. The neck circumference for each child was measured. The relationship between obtained surface doses and thyroid dose was studied using acrylic phantoms of various sizes and with holes of different depths. The ratios of hole-to-surface doses were used to convert patients' surface dose to thyroid dose. ImPACT software was utilized to calculate thyroid dose after applying the appropriate age correction factors. A paired t-test was performed to compare thyroid doses from our approach and ImPACT. The ratio of thyroid to surface dose was found to be 1.1. Thyroid doses ranged from 20 to 80 mGy. Comparison showed no statistical significance (p = 0.18). In addition, the average of surface dose variation along the z-axis in helical scans was studied and found to range between 5% (in 10 cm diameter phantom/24 mm collimation/pitch 1.0) and 8% (in 16 cm diameter phantom/12 mm collimation/pitch 0.7). We conclude that surface dose is an acceptable predictor for pediatric thyroid dose from CT. The uncertainty due to surface dose variability may be reduced if narrower collimation is used with a pitch factor close to 1.0. Also, the results did not show any effect of thyroid depth on the measured dose.

Tolerance of the Brachial Plexus to High-Dose Reirradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: achen5@kumc.edu; Yoshizaki, Taeko; Velez, Maria A.

Purpose: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. Methods and Materials: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculatedmore » by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). Results: The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus–related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). Conclusion: The development of brachial plexus–related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications.« less

Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria.

PubMed

White, Nicholas J; Duong, Tran T; Uthaisin, Chirapong; Nosten, François; Phyo, Aung P; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Jittamala, Podjanee; Chuthasmit, Kittiphum; Cheung, Ming S; Feng, Yiyan; Li, Ruobing; Magnusson, Baldur; Sultan, Marc; Wieser, Daniela; Xun, Xiaolei; Zhao, Rong; Diagana, Thierry T; Pertel, Peter; Leong, F Joel

2016-09-22

KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01753323 .).

Metabolic and skeletal effects of low and high doses of calcium acetate in patients with preterminal chronic renal failure.

PubMed

Phelps, Kenneth R; Stern, Marc; Slingerland, Alice; Heravi, Mahin; Strogatz, David S; Haqqie, Syed S

2002-01-01

Secondary hyperparathyroidism commonly evolves, as the glomerular filtration rate falls. The metabolic and skeletal effects of a possible remedy, calcium acetate, have not been studied in patients with preterminal chronic renal failure. Men with a mean creatinine clearance of approximately 30 ml/min took calcium acetate for 24 weeks at doses which provided 507 or 1,521 mg calcium/day with meals. Metabolic determinations were made at intervals of 4-8 weeks, and the bone mineral density (BMD) was measured at the beginning and at the end of the trial. The low-dose regimen produced no metabolic or skeletal effect. In subjects prescribed the high-dose regimen, the 24-hour urine phosphorus excretion fell from 0.53 mg/mg creatinine to values ranging from 0.34 to 0.41 mg/mg creatinine. The theoretical phosphorus threshold concentration rose by a maximum of 38.6%, and the serum phosphorus concentration did not change. The mean serum calcium concentration rose by a maximum of 7.2%. The mean fractional changes in parathyroid hormone and 1,25-dihydroxyvitamin D concentrations ranged from -27.0 to -39.6% and from -5.0 to -20.3%, respectively. The BMD increased at L1, L3, and L4. Calcium acetate prescribed to deliver 1,521 mg calcium/day with meals reduced parathyroid hormone and 1,25-dihydroxyvitamin D concentrations and increased lumbar BMD in men with preterminal chronic renal failure. Copyright 2002 S. Karger AG, Basel

Characteristics of an OSLD in the diagnostic energy range

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Senan, Rani M.; Hatab, Mustapha R.

2011-07-15

Purpose: Optically stimulated luminescence (OSL) dosimetry has been recently introduced in radiation therapy as a potential alternative to the thermoluminescent dosimeter (TLD) system. The aim of this study was to investigate the feasibility of using OSL point dosimeters in the energy range used in diagnostic imaging. Methods: NanoDot OSL dosimeters (OSLDs) were used in this study, which started with testing the homogeneity of a new packet of nanoDots. Reproducibility and the effect of optical treatment (bleaching) were then examined, followed by an investigation of the effect of accumulated dose on the OSLD indicated doses. OSLD linearity, angular dependence, and energymore » dependence were also studied. Furthermore, comparison with LiF:Mg,Ti TLD chips using standard CT dose phantoms at 80 and 120 kVp settings was performed. Results: Batch homogeneity showed a coefficient of variation of <5%. Single-irradiation measurements with bleaching after each OSL readout was found to be associated with a 3.3% reproducibility (one standard deviation measured with a 8 mGy test dose), and no systematic change in OSLDs sensitivity could be noted from measurement to measurement. In contrast, the multiple-irradiation readout without bleaching in between measurements was found to be associated with an uncertainty (using a 6 mGy test dose) that systematically increased with accumulated dose, reaching 42% at 82 mGy. Good linearity was shown by nanoDots under general x-ray, CT, and mammography units with an R{sup 2} > 0.99. The angular dependence test showed a drop of approximately 70% in the OSLD response at 90 deg. in mammography (25 kVp). With the general radiography unit, the maximum drop was 40% at 80 kVp and 20% at 120 kVp, and it was only 10% with CT at both 80 and 120 kVp. The energy dependence study showed a range of ion chamber-to-OSLDs ratios between 0.81 and 1.56, at the energies investigated (29-62 keV). A paired t-test for comparing the OSLDs and TLDs showed no significant variation (p > 0.1). Conclusions: OSLDs exhibited good batch homogeneity (<5%) and reproducibility (3.3%), as well as a linear response. In addition, they showed no statistically significant difference with TLDs in CT measurements (p > 0.1). However, high uncertainty (42%) in the dose estimate was found as a result of relatively high accumulated dose. Furthermore, nanoDots showed high angular dependence (up to 70%) in low kVp techniques. Energy dependence of about 60% was found, and correction factors were suggested for the range of energies investigated. Therefore, if angular and energy dependences are taken into consideration and the uncertainty associated with accumulated dose is avoided, OSLDs (nanoDots) can be suitable for use as point dosimeters in diagnostic settings.« less

Hormonal therapy for women with stage IA endometrial cancer of all grades.

PubMed

Park, Jeong-Yeol; Kim, Dae-Yeon; Kim, Tae-Jin; Kim, Jae Weon; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Bae, Duk-Soo; Nam, Joo-Hyun

2013-07-01

To estimate the oncologic and pregnancy outcomes after oral progestin treatment of women of reproductive age with stage IA endometrial adenocarcinoma with stage IA, grade 1 differentiation with superficial myometrial invasion or stage IA, grade 2-3 differentiation with or without superficial myometrial invasion. Medical records of 48 women (age 40 years or younger) with endometrioid adenocarcinoma of the uterus who met inclusion criteria and were treated conservatively with oral progestin were reviewed. Follow-up was performed primarily with imaging techniques followed by endometrial biopsy when indicated. The median age was 30 years (range, 23-40 years). Fourteen patients (29.2%) received daily oral megestrol acetate (median dose 160 mg per day, range 40-240 mg per day) and 34 (70.8%) received daily oral medroxyprogesterone acetate (median dose 500 mg per day, range 80-1,000 mg per day). Complete responses were observed for 37 patients (77.1%) after the median treatment duration of 10 months (range 3-20 months). Complete response rates were 76.5%, 73.9%, and 87.5% for patients with stage IA, grade 2-3 without myometrial invasion (n=17), for patients with stage IA, grade 1 with superficial myometrial invasion (n=23), and for patients with stage IA, grade 2-3 with superficial myometrial invasion (n=8), respectively (P=.731). Recurrence rates for 37 patients who achieved complete response after a median follow-up time of 48 months (range 7-136 months) were 23.1%, 47.1%, and 71.4%, respectively (P=.104). None experienced disease progression or died of the disease. Nine patients gave birth to 10 healthy newborns. Progestin treatment appears to be reasonably effective for patients with stage IA, grade 2-3 differentiation without myometrial invasion and patients with stage IA grade 1 differentiation with superficial myometrial invasion. III.

Relapsed or refractory primary central nervous system lymphoma radiosurgery: Report of the International Gamma Knife Research Foundation.

PubMed

Shin, Samuel M; Silverman, Joshua S; Bowden, Greg; Mathieu, David; Yang, Huai-Che; Lee, Cheng-Chia; Tam, Moses; Szelemej, Paul; Kaufmann, Anthony M; Cohen-Inbar, Or; Sheehan, Jason; Niranjan, Ajay; Lunsford, L Dade; Kondziolka, Douglas

2017-01-01

Stereotactic radiosurgery (SRS) can be used as part of multimodality management for patients with primary central nervous system lymphoma (PCNSL). The objective of this study is to evaluate outcomes of SRS for this disease. The International Gamma Knife Research Foundation identified 23 PCNSL patients who underwent SRS for either relapsed (intracerebral in-field or out-of-field tumor recurrences) or refractory disease from 1995-2014. All 23 patients presented with RPA Class I or II PCNSL, and were initially treated with a median of 7 cycles of methotrexate-based chemotherapy regimens (range, 3-26 cycles). Ten received prior whole brain radiation (WBRT) to a median dose of 43 Gy (range, 24-55 Gy). Sixteen presented with relapsed PCNSL, and seven presented with refractory disease. Twenty-three received 26 procedures of SRS. The median tumor volume was 4 cm 3 (range, 0.1-26 cm 3 ), and the median margin dose was 15 Gy (range, 8-20 Gy). Median follow-up from SRS was 11 months (interquartile range, 5.7-33.2 months). Twenty presented with treatment response to twenty-three tumors (12 complete, 11 partial). Fourteen patients relapsed or were refractory to salvage SRS, and local control was 95%, 91%, and 75% at 3, 6, and 12 months post SRS. Intracranial (in-field and out-of-field) and distant (systemic) PFS was 86%, 81%, and 55% at 3, 6, and 12 months post SRS. Toxicity of SRS was low, with one developing an adverse radiation effect requiring no additional intervention. Although methotrexate-based chemotherapy regimens with or without WBRT is the first-line management option for PCNSL, SRS may be used as an alternative option in properly selected patients with smaller relapsed or refractory PCNSL tumors.

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose.

PubMed

Bailey, George P; Wood, David M; Archer, John R H; Rab, Edmund; Flanagan, Robert J; Dargan, Paul I

2017-02-01

Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion. Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml -1 (-6.7 to -2.3) for the first infusion, +0.2 mg ml -1 (-0.9 to +0.4) for the second infusion and -0.3 mg ml -1 (-0.6 to +0.2) for third and fourth infusions. There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. © 2016 The British Pharmacological Society.

Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children.

PubMed

Englund, Janet A; Karron, Ruth A; Cunningham, Coleen K; Larussa, Philip; Melvin, Ann; Yogev, Ram; Handelsman, Ed; Siberry, George K; Thumar, Bhavanji; Schappell, Elizabeth; Bull, Catherine V; Chu, Helen Y; Schaap-Nutt, Anne; Buchholz, Ursula; Collins, Peter L; Schmidt, Alexander C

2013-11-19

Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined. HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10⁵ TCID₅₀ (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization. Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log₁₀ viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups. rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children. Copyright © 2013 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Juan; Beltran, Chris J., E-mail: beltran.chris@mayo.edu; Herman, Michael G.

Purpose: To quantitatively and systematically assess dosimetric effects induced by spot positioning error as a function of spot spacing (SS) on intensity-modulated proton therapy (IMPT) plan quality and to facilitate evaluation of safety tolerance limits on spot position. Methods: Spot position errors (PE) ranging from 1 to 2 mm were simulated. Simple plans were created on a water phantom, and IMPT plans were calculated on two pediatric patients with a brain tumor of 28 and 3 cc, respectively, using a commercial planning system. For the phantom, a uniform dose was delivered to targets located at different depths from 10 tomore » 20 cm with various field sizes from 2{sup 2} to 15{sup 2} cm{sup 2}. Two nominal spot sizes, 4.0 and 6.6 mm of 1 σ in water at isocenter, were used for treatment planning. The SS ranged from 0.5 σ to 1.5 σ, which is 2–6 mm for the small spot size and 3.3–9.9 mm for the large spot size. Various perturbation scenarios of a single spot error and systematic and random multiple spot errors were studied. To quantify the dosimetric effects, percent dose error (PDE) depth profiles and the value of percent dose error at the maximum dose difference (PDE [ΔDmax]) were used for evaluation. Results: A pair of hot and cold spots was created per spot shift. PDE[ΔDmax] is found to be a complex function of PE, SS, spot size, depth, and global spot distribution that can be well defined in simple models. For volumetric targets, the PDE [ΔDmax] is not noticeably affected by the change of field size or target volume within the studied ranges. In general, reducing SS decreased the dose error. For the facility studied, given a single spot error with a PE of 1.2 mm and for both spot sizes, a SS of 1σ resulted in a 2% maximum dose error; a SS larger than 1.25 σ substantially increased the dose error and its sensitivity to PE. A similar trend was observed in multiple spot errors (both systematic and random errors). Systematic PE can lead to noticeable hot spots along the field edges, which may be near critical structures. However, random PE showed minimal dose error. Conclusions: Dose error dependence for PE was quantitatively and systematically characterized and an analytic tool was built to simulate systematic and random errors for patient-specific IMPT. This information facilitates the determination of facility specific spot position error thresholds.« less

Feasibility of using two-dimensional array dosimeter for in vivo dose reconstruction via transit dosimetry.

PubMed

Chung, Heeteak; Li, Jonathan; Samant, Sanjiv

2011-04-08

Two-dimensional array dosimeters are commonly used to perform pretreatment quality assurance procedures, which makes them highly desirable for measuring transit fluences for in vivo dose reconstruction. The purpose of this study was to determine if an in vivo dose reconstruction via transit dosimetry using a 2D array dosimeter was possible. To test the accuracy of measuring transit dose distribution using a 2D array dosimeter, we evaluated it against the measurements made using ionization chamber and radiochromic film (RCF) profiles for various air gap distances (distance from the exit side of the solid water slabs to the detector distance; 0 cm, 30 cm, 40 cm, 50 cm, and 60 cm) and solid water slab thicknesses (10 cm and 20 cm). The backprojection dose reconstruction algorithm was described and evaluated. The agreement between the ionization chamber and RCF profiles for the transit dose distribution measurements ranged from -0.2% ~ 4.0% (average 1.79%). Using the backprojection dose reconstruction algorithm, we found that, of the six conformal fields, four had a 100% gamma index passing rate (3%/3 mm gamma index criteria), and two had gamma index passing rates of 99.4% and 99.6%. Of the five IMRT fields, three had a 100% gamma index passing rate, and two had gamma index passing rates of 99.6% and 98.8%. It was found that a 2D array dosimeter could be used for backprojection dose reconstruction for in vivo dosimetry.

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

PubMed

Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

2013-01-15

We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

PubMed Central

2013-01-01

Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. Trial registration ClinicalTrials.gov number:NCT00978211 PMID:23320604

Inoculum Effects of Ceftobiprole, Daptomycin, Linezolid, and Vancomycin with Staphylococcus aureus and Streptococcus pneumoniae at Inocula of 105 and 107 CFU Injected into Opposite Thighs of Neutropenic Mice

PubMed Central

Lee, Dong-Gun; Murakami, Yoichi; Andes, David R.

2013-01-01

Reduced bactericidal efficacy at a high inoculum is known as the inoculum effect (IE). We used neutropenic mice to compare the IEs of ceftobiprole (CFB), daptomycin (DAP), linezolid (LZD), and vancomycin (VAN) against 6 to 9 strains of Staphylococcus aureus and 4 strains of Streptococcus pneumoniae at 2 inocula in opposite thighs of the same mice. Neutropenic mice had 104.5 to 105.7 CFU/thigh (low inoculum [LI]) in one thigh and 106.4 to 107.2 CFU/thigh (high inoculum [HI]) in the opposite thigh when treated for 24 h with subcutaneous (s.c.) doses every 12 h of DAP at 0.024 to 100 mg/kg of body weight and LZD at 0.313 to 320 mg/kg and s.c. doses every 6 h of CFB at 0.003 to 160 mg/kg and VAN at 0.049 to 800 mg/kg. Dose-response data were analyzed by a maximum effect (Emax) model using nonlinear regression. Static doses for each drug and at each inoculum were calculated, and the difference between HI and LI (IE index) gave the magnitude of IE for each drug-organism combination. Mean (range) IE indexes of S. aureus were 2.9 (1.7 to 4.6) for CFB, 4.1 (2.6 to 9.3) for DAP, 4.6 (1.7 to 7.1) for LZD, and 10.1 (6.3 to 20.3) for VAN. In S. pneumoniae, the IE indexes were 2.5 (1.3 to 3.3) for CFB, 2.0 (1.6 to 2.8) for DAP, 1.9 (1.7 to 2.2) for LZD, and 1.5 (0.8 to 3.2) for VAN; these values were similar for all drugs. In S. aureus, the IE was much larger with VAN than with CFB, DAM, and LZD (P < 0.05). An in vivo time course of vancomycin activity showed initiation of killing at 4- to 16-fold-higher doses at HI than at LI despite similar initial growth of controls. PMID:23295932

SU-F-J-145: MRI-Guided Interventional Boost Radiotherapy for Rectal Cancer: Investigating the Feasibility of Adapting the Anatomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleijnen, J J E; Couwenberg, A M; Asselen, B van

Purpose: The recent development of an MRI-linac allows adaptation of treatments to the anatomy of the moment. This anatomy, in turn, could be altered into a more favorable situation for radiotherapy purposes. The purpose of this study is to investigate the potential dosimetric benefits of manipulating rectal anatomy in MRI-guided interventional external-beam radiotherapy for rectal cancer. Methods: For this retrospective analysis, four patients (1M/3F) diagnosed with rectal cancer were included. These underwent MR-imaging using sonography transmission gel as endorectal contrast at time of diagnosis and standard, non-contrast, MR-imaging prior to radiotherapy planning. In the contrast scan, the rectum is inflatedmore » by the inserted contrast gel, thereby potentially increasing the distance between tumor and the organs-at-risk (OAR). Both anatomies were delineated and 7- beam IMRT-plans were calculated for both situations (RT-standard and RT-inflated), using in-house developed treatment planning software. Each plan was aimed to deliver 15Gy to the planning target volume (PTV; tumor+3mm margin) with a D99>95% and Dmax<120% of the planned dose. The D2cc dose to the OAR were then compared for both situations. Results: At equal (or better) target coverage, we found a mean reduction in D2cc of 4.1Gy/237% [range 2.6Gy–6.3Gy/70%–621%] for the bladder and of 2.0Gy/145% [range −0.7Gy–7.9Gy/−73%–442%] for the small-bowel, for the RT-inflated compared to the RT-standard plans. For the three female patients, a reduction in D2cc of 5.2Gy/191% [range 3.2Gy–9.2Gy/44%–475%] for the gynecological organs was found. We found all D2cc doses to be better for the RT-inflated plans, except for one patient for whom the bladder D2cc dose was slightly increased. Conclusion: Reduction of OAR dose by manipulation of anatomy is feasible. Inflation of the rectum results in more distance between OAR and PTV. This leads to a substantial reduction in dose to OAR at equal or better target coverage.« less

Clinical prognostic factors and grading system for rib fracture following stereotactic body radiation therapy (SBRT) in patients with peripheral lung tumors.

PubMed

Kim, Su Ssan; Song, Si Yeol; Kwak, Jungwon; Ahn, Seung Do; Kim, Jong Hoon; Lee, Jung Shin; Kim, Woo Sung; Kim, Sang-We; Choi, Eun Kyung

2013-02-01

Several studies reported rib fractures following stereotactic body radiation therapy (SBRT) for peripheral lung tumors. We tried to investigate risk factors and grading system for rib fractures after SBRT. Of 375 primary or metastatic lung tumors (296 patients) which were treated with SBRT at the Asan Medical Center (2006-2009), 126 lesions (118 patients) were adjacent to the chest-wall (<1cm) and followed-up with chest computed tomography (CT) for >6 months; these were investigated in the present retrospective study. Three to four fractional doses of 10-20 Gy were delivered to 85-90% iso-dose volume of the isocenter dose. Rib fracture grade was defined from follow-up CT scans as the appearance of a fracture line (Gr1), dislocation of the fractured rib by more than half the rib diameter (Gr2), or the appearance of adjacent soft tissue edema (Gr3). Chest wall pain was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Correlations between dose-volume data and the development of rib fracture were then analyzed. The Kaplan-Meier method, log-rank tests, and chi-square tests were used for statistical analysis. The median age of the patients was 69 years (range: 19-90). Over a median follow-up period of 22 months (range: 7-62), 48 cases of rib fracture were confirmed. Median time to rib fracture was 17 months (range: 4-52). The 2-year actuarial risk of rib fracture was 42.4%. Maximal grade was Gr1 (n=28), Gr2 (n=8), or Gr3 (n=15). The incidence of moderate to severe chest wall pain (CTCAE Gr ≥ 2) increased with maximal fracture grade (17.5% for Gr0-1 and 60.9% for Gr2-3; p<0.001). Multivariate analysis identified female gender, lateral location, and the dose to the 8cc of the chest wall as significant prognostic factors. Female gender and lateral tumor location were clinical risk factors for rib fracture in the present study. Efforts to decrease chest wall dose should be made to reduce the risk of the rib fracture, particularly in high-risk patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

IMRT and RapidArc commissioning of a TrueBeam linear accelerator using TG-119 protocol cases.

PubMed

Wen, Ning; Zhao, Bo; Kim, Jinkoo; Chin-Snyder, Karen; Bellon, Maria; Glide-Hurst, Carri; Barton, Kenneth; Chen, Daiquan; Chetty, Indrin J

2014-09-08

The purpose of this study is to evaluate the overall accuracy of intensity-modulated radiation therapy (IMRT) and RapidArc delivery using both flattening filter (FF) and flattening filter-free (FFF) modalities based on test cases developed by AAPM Task Group 119. Institutional confidence limits (CLs) were established as the baseline for patient specific treatment plan quality assurance (QA). The effects of gantry range, gantry speed, leaf speed, dose rate, as well as the capability to capture intentional errors, were evaluated by measuring a series of Picket Fence (PF) tests using the electronic portal imaging device (EPID) and EBT3 films. Both IMRT and RapidArc plans were created in a Solid Water phantom (30 × 30 × 15 cm3) for the TG-119 test cases representative of normal clinical treatment sites for all five photon energies (6X, 10X, 15X, 6X-FFF, 10X-FFF) and the Exact IGRT couch was included in the dose calculation. One high-dose point in the PTV and one low-dose point in the avoidance structure were measured with an ion chamber in each case for each energy. Similarly, two GAFCHROMIC EBT3 films were placed in the coronal planes to measure planar dose distributions in both high- and low-dose regions. The confidence limit was set to have 95% of the measured data fall within the tolerance. The mean of the absolute dose deviation for variable dose rate and gantry speed during RapidArc delivery was within 0.5% for all energies. The corresponding results for leaf speed tests were all within 0.4%. The combinations of dynamic leaf gap (DLG) and MLC transmission factor were optimized based on the ion chamber measurement results of RapidArc delivery for each energy. The average 95% CLs for the high-dose point in the PTV were 0.030 ± 0.007 (range, 0.022-0.038) for the IMRT plans and 0.029 ± 0.011 (range, 0.016-0.043) for the RapidArc plans. For low-point dose in the avoidance structures, the CLs were 0.029 ± 0.006 (range, 0.024-0.039) for the IMRT plans and 0.027 ± 0.013 (range, 0.017-0.047) for the RapidArc plans. The average 95% CLs using 3%/3 mm gamma criteria in the high-dose region were 5.9 ± 2.7 (range, 1.4-8.6) and 3.9 ± 2.9 (range, 1.5-8.8) for IMRT and RapidArc plans, respectively. The average 95% CLs in the low-dose region were 5.3 ± 2.6 (range, 1.2-7.4) and 3.7 ± 2.8 (range, 1.8-8.3) for IMRT and RapidArc plans, respectively. Based on ion chamber, as well as film measurements, we have established CLs values to ensure the high precision of IMRT and RapidArc delivery for both FF and FFF modalities.

Optimization of the sensitivity/doses relationship for a bench-top EDXRF system used for in vivo quantification of gold nanoparticles.

PubMed

Santibáñez, M; Saavedra, R; Vásquez, M; Malano, F; Pérez, P; Valente, M; Figueroa, R G

2017-11-01

The present work is devoted to optimizing the sensitivity-doses relationship of a bench-top EDXRF system, with the aim of achieving a detection limit of 0.010mg/ml of gold nanoparticles in tumor tissue (clinical values expected), for doses below 10mGy (value fixed for in vivo application). Tumor phantoms of 0.3cm 3 made of a suspension of gold nanoparticles (15nm AurovistTM, Nanoprobes Inc.) were studied at depths of 0-4mm in a tissue equivalent cylindrical phantom. The optimization process was implemented configuring several tube voltages and aluminum filters, to obtain non-symmetrical narrow spectra with fixed FWHM of 5keV and centered among the 11.2-20.3keV. The used statistical figure of merit was the obtained sensitivity (with each spectrum at each depth) weighted by the delivered surface doses. The detection limit of the system was determined measuring several gold nanoparticles concentrations ranging from 0.0010 to 5.0mg/ml and a blank sample into tumor phantoms, considering a statistical fluctuation within 95% of confidence. The results show the possibility of obtaining a detection limit for gold nanoparticles concentrations around 0.010mg/ml for surface tumor phantoms requiring doses around 2mGy. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro dose measurements in a human cadaver with abdomen/pelvis CT scans.

PubMed

Zhang, Da; Padole, Atul; Li, Xinhua; Singh, Sarabjeet; Khawaja, Ranish Deedar Ali; Lira, Diego; Liu, Tianyu; Shi, Jim Q; Otrakji, Alexi; Kalra, Mannudeep K; Xu, X George; Liu, Bob

2014-09-01

To present a study of radiation dose measurements with a human cadaver scanned on a clinical CT scanner. Multiple point dose measurements were obtained with high-accuracy Thimble ionization chambers placed inside the stomach, liver, paravertebral gutter, ascending colon, left kidney, and urinary bladder of a human cadaver (183 cm in height and 67.5 kg in weight) whose abdomen/pelvis region was scanned repeatedly with a multidetector row CT. The flat energy response and precision of the dosimeters were verified, and the slight differences in each dosimeter's response were evaluated and corrected to attain high accuracy. In addition, skin doses were measured for radiosensitive organs outside the scanned region with OSL dosimeters: the right eye, thyroid, both nipples, and the right testicle. Three scan protocols were used, which shared most scan parameters but had different kVp and mA settings: 120-kVp automA, 120-kVp 300 mA, and 100-kVp 300 mA. For each protocol three repeated scans were performed. The tube starting angle (TSA) was found to randomly vary around two major conditions, which caused large fluctuations in the repeated point dose measurements: for the 120-kVp 300 mA protocol this angle changed from approximately 110° to 290°, and caused 8%-25% difference in the point dose measured at the stomach, liver, colon, and urinary bladder. When the fluctuations of the TSA were small (within 5°), the maximum coefficient of variance was approximately 3.3%. The soft tissue absorbed doses averaged from four locations near the center of the scanned region were 27.2±3.3 and 16.5±2.7 mGy for the 120 and 100-kVp fixed-mA scans, respectively. These values were consistent with the corresponding size specific dose estimates within 4%. The comparison of the per-100-mAs tissue doses from the three protocols revealed that: (1) dose levels at nonsuperficial locations in the TCM scans could not be accurately deduced by simply scaling the fix-mA doses with local mA values; (2) the general power law relationship between dose and kVp varied from location to location, with the power index ranged between 2.7 and 3.5. The averaged dose measurements at both nipples, which were about 0.6 cm outside the prescribed scan region, ranged from 23 to 27 mGy at the left nipple, and varied from 3 to 20 mGy at the right nipple over the three scan protocols. Large fluctuations over repeated scans were also observed, as a combined result of helical scans of large pitch (1.375) and small active areas of the skin dosimeters. In addition, the averaged skin dose fell off drastically with the distance to the nearest boundary of the scanned region. This study revealed the complexity of CT dose fluctuation and variation with a human cadaver.

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Carolyn W., E-mail: carolyn.taylor@ctsu.ox.ac.uk; Wang, Zhe; Macaulay, Elizabeth

Purpose: Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Methods and Materials: Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this “mean heart dose.” Results: In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28more » countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Conclusions: Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose.« less

Effective radiation dose of ProMax 3D cone-beam computerized tomography scanner with different dental protocols.

PubMed

Qu, Xing-min; Li, Gang; Ludlow, John B; Zhang, Zu-yan; Ma, Xu-chen

2010-12-01

The aim of this study was to compare effective doses resulting from different scan protocols for cone-beam computerized tomography (CBCT) using International Commission on Radiological Protection (ICRP) 1990 and 2007 calculations of dose. Average tissue-absorbed dose, equivalent dose, and effective dose for a ProMax 3D CBCT with different dental protocols were calculated using thermoluminescent dosimeter chips in a human equivalent phantom. Effective doses were derived using ICRP 1990 and the superseding 2007 recommendations. Effective doses (ICRP 2007) for default patient sizes from small to large ranged from 102 to 298 μSv. The coefficient of determination (R(2)) between tube current and effective dose (ICRP 2007) was 0.90. When scanning with lower resolution settings, the effective doses were reduced significantly (P < .05). ProMax 3D can provide a wide range of radiation dose levels. Reduction in radiation dose can be achieved when using lower settings of exposure parameters. Copyright © 2010 Mosby, Inc. All rights reserved.

Single-dose pharmacokinetic properties of esomeprazole in children aged 1 - 11 years with endoscopically proven GERD: a randomized, open-label study.

PubMed

Youssef, Nader N; Tron, Eduardo; Tolia, Vasundhara; Hamer-Maansson, Jennifer E; Lundborg, Per; Illueca, Marta

2014-11-01

To assess the overall exposure after a single dose of esomeprazole in children with gastroesophageal reflux disease (GERD). Oral esomeprazole administered as an intact capsule with 30 - 180 mL of water, or as an opened capsule mixed with as much as 1 tablespoon of applesauce followed by 30 - 180 mL of water. In this randomized, open-label study of children aged 1 - 11 years with endoscopically proven GERD, patients weighing 8 - < 20 kg were randomized to a single 5- or 10-mg oral dose of esomeprazole, and patients weighing >= 20 kg were randomized to a single 10- or 20-mg oral dose of esomeprazole. Esomeprazole exposure (AUC(0-∞)), AUC from zero to last measurable concentration (AUC(0-t)), maximum plasma concentration (C(max)), time to C(max) (t(max)), terminal-phase half-life, apparent oral clearance, and apparent volume of distribution were determined. 28 patients were randomized to receive esomeprazole: 14 patients weighing 8 to < 20 kg received esomeprazole 5 mg (n = 7) or 10 mg (n = 7), and 14 patients weighing ≥20 kg received esomeprazole 10 mg (n = 6) or 20 mg (n = 8). Children weighing 8 - < 20 kg had a 1.8-fold higher exposure with the 10-mg vs. 5-mg dose (AUC(0-∞), 1.32 vs. 0.73 μmol·h/L, respectively); children weighing ≥ 20 kg had a 4.4-fold higher exposure with the 20-mg vs. 10-mg dose (AUC(0-∞), 3.06 vs. 0.69 μmol·h/L). C(max) was 2.2-fold higher for the 10-mg vs. 5-mg dose (8 to < 20 kg) and 2.4-fold higher for the 20-mg vs.10-mg dose (>= 20 kg). The pharmacokinetics of single-dose esomeprazole were dose-dependent in children weighing >= 20 kg but not in children weighing 8 to < 20 kg.

Simplified method for creating a density-absorbed dose calibration curve for the low dose range from Gafchromic EBT3 film.

PubMed

Gotanda, Tatsuhiro; Katsuda, Toshizo; Gotanda, Rumi; Kuwano, Tadao; Akagawa, Takuya; Tanki, Nobuyoshi; Tabuchi, Akihiko; Shimono, Tetsunori; Kawaji, Yasuyuki

2016-01-01

Radiochromic film dosimeters have a disadvantage in comparison with an ionization chamber in that the dosimetry process is time-consuming for creating a density-absorbed dose calibration curve. The purpose of this study was the development of a simplified method of creating a density-absorbed dose calibration curve from radiochromic film within a short time. This simplified method was performed using Gafchromic EBT3 film with a low energy dependence and step-shaped Al filter. The simplified method was compared with the standard method. The density-absorbed dose calibration curves created using the simplified and standard methods exhibited approximately similar straight lines, and the gradients of the density-absorbed dose calibration curves were -32.336 and -33.746, respectively. The simplified method can obtain calibration curves within a much shorter time compared to the standard method. It is considered that the simplified method for EBT3 film offers a more time-efficient means of determining the density-absorbed dose calibration curve within a low absorbed dose range such as the diagnostic range.

Simplified method for creating a density-absorbed dose calibration curve for the low dose range from Gafchromic EBT3 film

PubMed Central

Gotanda, Tatsuhiro; Katsuda, Toshizo; Gotanda, Rumi; Kuwano, Tadao; Akagawa, Takuya; Tanki, Nobuyoshi; Tabuchi, Akihiko; Shimono, Tetsunori; Kawaji, Yasuyuki

2016-01-01

Radiochromic film dosimeters have a disadvantage in comparison with an ionization chamber in that the dosimetry process is time-consuming for creating a density-absorbed dose calibration curve. The purpose of this study was the development of a simplified method of creating a density-absorbed dose calibration curve from radiochromic film within a short time. This simplified method was performed using Gafchromic EBT3 film with a low energy dependence and step-shaped Al filter. The simplified method was compared with the standard method. The density-absorbed dose calibration curves created using the simplified and standard methods exhibited approximately similar straight lines, and the gradients of the density-absorbed dose calibration curves were −32.336 and −33.746, respectively. The simplified method can obtain calibration curves within a much shorter time compared to the standard method. It is considered that the simplified method for EBT3 film offers a more time-efficient means of determining the density-absorbed dose calibration curve within a low absorbed dose range such as the diagnostic range. PMID:28144120

SU-F-T-157: Physics Considerations Regarding Dosimetric Accuracy of Analytical Dose Calculations for Small Field Proton Therapy: A Monte Carlo Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, C; Nanjing University of Aeronautics and Astronautics, Nanjing; Daartz, J

Purpose: To evaluate the accuracy of dose calculations by analytical dose calculation methods (ADC) for small field proton therapy in a gantry based passive scattering facility. Methods: 50 patients with intra-cranial disease were evaluated in the study. Treatment plans followed standard prescription and optimization procedures of proton stereotactic radiosurgery. Dose distributions calculated with the Monte Carlo (MC) toolkit TOPAS were used to represent delivered treatments. The MC dose was first adjusted using the output factor (OF) applied clinically. This factor is determined from the field size and the prescribed range. We then introduced a normalization factor to measure the differencemore » in mean dose between the delivered dose (MC dose with OF) and the dose calculated by ADC for each beam. The normalization was determined by the mean dose of the center voxels of the target area. We compared delivered dose distributions and those calculated by ADC in terms of dose volume histogram parameters and beam range distributions. Results: The mean target dose for a whole treatment is generally within 5% comparing delivered dose (MC dose with OF) and ADC dose. However, the differences can be as great as 11% for shallow and small target treated with a thick range compensator. Applying the normalization factor to the MC dose with OF can reduce the mean dose difference to less than 3%. Considering range uncertainties, the generally applied margins (3.5% of the prescribed range + 1mm) to cover uncertainties in range might not be sufficient to guarantee tumor coverage. The range difference for R90 (90% distal dose falloff) is affected by multiple factors, such as the heterogeneity index. Conclusion: This study indicates insufficient accuracy calculating proton doses using ADC. Our results suggest that uncertainties of target doses are reduced using MC techniques, improving the dosimetric accuracy for proton stereotactic radiosurgery. The work was supported by NIH/NCI under CA U19 021239. CG was partially supported by the Chinese Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087).« less

Etirinotecan pegol administration is associated with lower incidences of neutropenia compared to irinotecan administration.

PubMed

Sy, S Kenneth; Sweeney, Theresa D; Ji, Chunmei; Hoch, Ute; Eldon, Michael A

2017-01-01

The relationship between incidences of neutropenia and 10-hydroxy-7-ethyl camptothecin (SN38) exposure was explored using SN38 pharmacokinetic and neutrophil count data from toxicology studies of etirinotecan pegol (EP) and irinotecan in beagle dogs. Dogs received four weekly intravenous infusions of either vehicle control (n = 22), EP (6, 15, 20, 25, 40/25 mg/kg; n = 3-9 dogs/dose group/sex; n = 48), or irinotecan (20 or 25 mg/kg n = 3-4 dogs/dose group/sex; n = 14). Blood samples were collected up to 50 days post-dose for characterization of SN38 pharmacokinetics. Two separate models were created describing SN38 concentration time profiles after either irinotecan or EP administrations to project the AUC 0-168h after Day 1 and Day 22 doses. The relationship between incidence of neutropenia and SN38 exposure was explored using logistic regression. The incidence of neutropenia in dogs receiving weekly doses of irinotecan or EP was strongly correlated with maximum plasma SN38 concentration (C max ), but not SN38 area under the concentration-time curve (AUC). Neutropenia occurred in approximately 80% of dogs receiving irinotecan (mean SN38 C max of 13.5 and 26.3 ng/mL for 20 and 25 mg/kg, respectively). No neutropenia occurred in dogs receiving EP at doses up to and including 25 mg/kg (mean SN38 C max of 3.4 and 4.9 ng/mL for 20 and 25 mg/kg, respectively), despite 2.5-3.6 times greater SN38 AUC after EP compared to irinotecan at equivalent doses. EP administration avoids both high SN38 C max values and development of dose-limiting neutropenia observed after irinotecan, while maintaining greater and sustained SN38 exposure between doses.

Equivalent square formula for determining the surface dose of rectangular field from 6 MV therapeutic photon beam.

PubMed

Apipunyasopon, Lukkana; Srisatit, Somyot; Phaisangittisakul, Nakorn

2013-09-06

The purpose of the study was to investigate the use of the equivalent square formula for determining the surface dose from a rectangular photon beam. A 6 MV therapeutic photon beam delivered from a Varian Clinac 23EX medical linear accelerator was modeled using the EGS4nrc Monte Carlo simulation package. It was then used to calculate the dose in the build-up region from both square and rectangular fields. The field patterns were defined by various settings of the X- and Y-collimator jaw ranging from 5 to 20 cm. Dose measurements were performed using a thermoluminescence dosimeter and a Markus parallel-plate ionization chamber on the four square fields (5 × 5, 10 × 10, 15 × 15, and 20 × 20 cm2). The surface dose was acquired by extrapolating the build-up doses to the surface. An equivalent square for a rectangular field was determined using the area-to-perimeter formula, and the surface dose of the equivalent square was estimated using the square-field data. The surface dose of square field increased linearly from approximately 10% to 28% as the side of the square field increased from 5 to 20 cm. The influence of collimator exchange on the surface dose was found to be not significant. The difference in the percentage surface dose of the rectangular field compared to that of the relevant equivalent square was insignificant and can be clinically neglected. The use of the area-to-perimeter formula for an equivalent square field can provide a clinically acceptable surface dose estimation for a rectangular field from a 6 MV therapy photon beam.